Mediator kinase module and human tumorigenesis

Critical Reviews in Biochemistry and Molecular Biology

Volumn 50, Issue 5, 2015, Pages 393-426

  Clark, Alison D ^a   Oldenbroek, Marieke ^a   Boyer, Thomas G ^a  

^a University of Texas Health Science Center   (United States)

Author keywords

Cancer; development; Mediator; RNA polymerase II transcription; signal transduction

Indexed keywords

1,25 DIHYDROXYVITAMIN D3 14 EPI DERIVATIVE; BETA CATENIN; CALCITRIOL DERIVATIVE; CYCLIN C; CYCLIN DEPENDENT KINASE 8; CYCLIN DEPENDENT KINASE INHIBITOR; MALTONIS; MEDIATOR COMPLEX; MEDIATOR KINASE MODULE; MEDIATOR KINASE MODULE MED12 SUBUNIT; MEDIATOR KINASE MODULE MED13 SUBUNIT; MICRORNA; MICRORNA 107; MICRORNA 26B; OXYGEN; PHOSPHOTRANSFERASE; PROTEIN P21; PROTEIN P27; SENEXIN A; SORAFENIB; TRANSCRIPTION FACTOR E2F1; TRANSFORMING GROWTH FACTOR BETA; TX 522; TX 527; UNCLASSIFIED DRUG; WNT PROTEIN; WOGONIN; CCNC PROTEIN, HUMAN; CDK8 PROTEIN, HUMAN; MED12 PROTEIN, HUMAN; MED13 PROTEIN, HUMAN; PROTEIN SUBUNIT;

ACUTE LYMPHOBLASTIC LEUKEMIA; BREAST CANCER; BREAST FIBROEPITHELIAL TUMOR; BREAST TUMOR; CANCER RESISTANCE; CARCINOGENESIS; CELL CYCLE REGULATION; CELL DIFFERENTIATION; CELL FATE; CELL FUNCTION; COLORECTAL CANCER; DISEASE ASSOCIATION; ENDOMETRIUM CANCER; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INACTIVATION; ENZYME REGULATION; ENZYME SUBUNIT; G1 PHASE CELL CYCLE CHECKPOINT; G2 PHASE CELL CYCLE CHECKPOINT; GENE CONTROL; HOMEOSTASIS; HUMAN; HUMAN DEVELOPMENT; INNATE IMMUNITY; MELANOMA; NEOPLASM; NONHUMAN; OSTEOSARCOMA; PARALOGY; PHYSIOLOGICAL PROCESS; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; UTERUS MYOMA; ANIMAL; BIOLOGICAL MODEL; CHEMISTRY; GENE EXPRESSION REGULATION; METABOLISM; PROTEIN CONFORMATION; PROTEIN MULTIMERIZATION; PROTEIN SUBUNIT;

ANIMALS; CARCINOGENESIS; CYCLIN C; CYCLIN-DEPENDENT KINASE 8; GENE EXPRESSION REGULATION, DEVELOPMENTAL; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MEDIATOR COMPLEX; MODELS, BIOLOGICAL; PROTEIN CONFORMATION; PROTEIN MULTIMERIZATION; PROTEIN SUBUNITS;

EID: 84944178042     PISSN: 10409238     EISSN: 15497798     Source Type: Journal    
DOI: 10.3109/10409238.2015.1064854     Document Type: Review

References (340)

1. Adegbola A, Musante L, Callewaert B, et al. (2015). Redefining the MED13L syndrome. Eur J Hum Genet. [Epub ahead of print]. doi: 10.1038/ejhg.2015.26
2. Adler AS, McCleland ML, Truong T, et al. (2012). CDK8 maintains tumor dedifferentiation and embryonic stem cell pluripotency. Cancer Res 72: 2129-39
3. Ahn SM, Jang SJ, Shim JH, et al. (2014). Genomic portrait of resectable hepatocellular carcinomas: implications of RB1 and FGF19 aberrations for patient stratification. Hepatology 60: 1972-82
4. Akoulitchev S, Chuikov S, Reinberg D. (2000). TFIIH is negatively regulated by cdk8-containing mediator complexes. Nature 407: 102-6
5. Alarcon C, Zaromytidou AI, Xi Q, et al. (2009). Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways. Cell 139: 757-69
6. Allen BL, Taatjes DJ. (2015). The Mediator complex: a central integrator of transcription. Nat Rev Mol Cell Biol 16: 155-66
7. Ansari SA, Morse RH. (2013). Mechanisms of Mediator complex action in transcriptional activation. Cell Mol Life Sci 70: 2743-56
8. Aragon E, Goerner N, Zaromytidou AI, et al. (2011). A Smad action turnover switch operated by WW domain readers of a phosphoserine code. Genes Dev 25: 1275-88
9. Asadollahi R, Oneda B, Sheth F, et al. (2013). Dosage changes of MED13L further delineate its role in congenital heart defects and intellectual disability. Eur J Hum Genet 21: 1100-4
10. Assie G, Letouze E, Fassnacht M, et al. (2014). Integrated genomic characterization of adrenocortical carcinoma. Nat Genet 46: 607-12
11. Asturias FJ, Jiang YW, Myers LC, et al. (1999). Conserved structures of mediator and RNA polymerase II holoenzyme. Science 283: 985-7
12. Baca SC, Prandi D, Lawrence MS, et al. (2013). Punctuated evolution of prostate cancer genomes. Cell 153: 666-77
13. Bancerek J, Poss ZC, Steinparzer I, et al. (2013). CDK8 kinase phosphorylates transcription factor STAT1 to selectively regulate the interferon response. Immunity 38: 250-62
14. Banerji S, Cibulskis K, Rangel-Escareno C, et al. (2012). Sequence analysis of mutations and translocations across breast cancer subtypes. Nature 486: 405-9
15. Banyai G, Lopez MD, Szilagyi Z, Gustafsson CM. (2014). Mediator can regulate mitotic entry and direct periodic transcription in fission yeast. Mol Cell Biol 34: 4008-18
16. Barbieri CE, Baca SC, Lawrence MS, et al. (2012). Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat Genet 44: 685-9
17. Barretina J, Taylor BS, Banerji S, et al. (2010). Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nat Genet 42: 715-21
18. Behrens J, Lustig B. (2004). The Wnt connection to tumorigenesis. Int J Dev Biol 48: 477-87
19. Belakavadi M, Fondell JD. (2010). Cyclin-dependent kinase 8 positively cooperates with Mediator to promote thyroid hormone receptor-dependent transcriptional activation. Mol Cell Biol 30: 2437-48
20. Berger MF, Hodis E, Heffernan TP, et al. (2012). Melanoma genome sequencing reveals frequent PREX2 mutations. Nature 485: 502-6
21. Berk AJ. (2012). Yin and yang of mediator function revealed by human mutants. Proc Natl Acad Sci USA 109: 19519-20
22. Bernecky C, Grob P, Ebmeier CC, et al. (2011). Molecular architecture of the human Mediator-RNA polymerase II-TFIIF assembly. PLoS Biol 9: e1000603
23. Bertsch E, Qiang W, Zhang Q, et al. (2014). MED12 and HMGA2 mutations: two independent genetic events in uterine leiomyoma and leiomyosarcoma. Mod Pathol 27: 1144-53
24. Bhoite LT, Yu Y, Stillman DJ. (2001). The Swi5 activator recruits the Mediator complex to the HO promoter without RNA polymerase II. Genes Dev 15: 2457-69
25. Biomarkers Definitions Working Group. (2001). Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69: 89-95
26. Bondi J, Husdal A, Bukholm G, et al. (2005). Expression and gene amplification of primary (A, B1, D1, D3, and E) and secondary (C and H) cyclins in colon adenocarcinomas and correlation with patient outcome. J Clin Pathol 58: 509-14
27. Borggrefe T, Davis R, Erdjument-Bromage H, et al. (2002). A complex of the Srb8, -9, -10, and -11 transcriptional regulatory proteins from yeast. J Biol Chem 277: 44202-7
28. Bourbon HM. (2008). Comparative genomics supports a deep evolutionary origin for the large, four-module transcriptional mediator complex. Nucleic Acids Res 36: 3993-4008
29. Boyer TG, Martin ME, Lees E, et al. (1999). Mammalian Srb/Mediator complex is targeted by adenovirus E1A protein. Nature 399: 276-9
30. Buck V, Ng SS, Ruiz-Garcia AB, et al. (2004). Fkh2p and Sep1p regulate mitotic gene transcription in fission yeast. J Cell Sci 117: 5623-32
31. Bulun SE. (2013). Uterine fibroids. N Engl J Med 369: 1344-55
32. Burnett JC, Rossi JJ. (2012). RNA-based therapeutics: current progress and future prospects. Chem Biol 19: 60-71
33. Cafiero C, Marangi G, Orteschi D, et al. (2015). Novel de novo heterozygous loss-of-function variants in MED13L and further delineation of the MED13L haploinsufficiency syndrome. Eur J Hum Genet. [Epub ahead of print]. doi: 10.1038/ejhg.2015.19
34. Cai G, Imasaki T, Takagi Y, Asturias FJ. (2009). Mediator structural conservation and implications for the regulation mechanism. Structure 17: 559-67
35. Cancer Genome Atlas Network. (2012a). Comprehensive molecular characterization of human colon and rectal cancer. Nature 487: 330-7
36. Cancer Genome Atlas Network. (2012b). Comprehensive molecular portraits of human breast tumours. Nature 490: 61-70
37. Cancer Genome Atlas Research Network., Kandoth C, Schultz N, et al. (2013). Integrated genomic characterization of endometrial carcinoma. Nature 497: 67-73
38. Cancer Genome Atlas Research Network. (2011). Integrated genomic analyses of ovarian carcinoma. Nature 474: 609-15
39. Cancer Genome Atlas Research Network. (2012). Comprehensive genomic characterization of squamous cell lung cancers. Nature 489: 519-25
40. Cancer Genome Atlas Research Network. (2013). Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature 499: 43-9
41. Cancer Genome Atlas Research Network. (2014a). Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513: 202-9
42. Cancer Genome Atlas Research Network. (2014b). Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507: 315-22
43. Cancer Genome Atlas Research Network. (2014c). Comprehensive molecular profiling of lung adenocarcinoma. Nature 511: 543-50
44. Cani AK, Hovelson DH, McDaniel AS, et al. (2015). Next-Gen sequencing exposes frequent MED12 mutations and actionable therapeutic targets in phyllodes tumors. Mol Cancer Res 13: 613-19
45. Cantin GT, Stevens JL, Berk AJ. (2003). Activation domain-mediator interactions promote transcription preinitiation complex assembly on promoter DNA. Proc Natl Acad Sci USA 100: 12003-8
46. Carlson M. (1997). Genetics of transcriptional regulation in yeast: connections to the RNA polymerase II CTD. Annu Rev Cell Dev Biol 13: 1-23
47. Carlsten JO, Zhu X, Gustafsson CM. (2013). The multitalented Mediator complex. Trends Biochem Sci 38: 531-7
48. Carrera I, Janody F, Leeds N, et al. (2008). Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13. Proc Natl Acad Sci USA 105: 6644-9
49. Chadick JZ, Asturias FJ. (2005). Structure of eukaryotic Mediator complexes. Trends Biochem Sci 30: 264-71
50. Chan CH, Li CF, Yang WL, et al. (2012). The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis. Cell 149: 1098-111
51. Chen M, Carkner R, Buttyan R. (2011). The hedgehog/Gli signaling paradigm in prostate cancer. Expert Rev Endocrinol Metab 6: 453-67
52. Chen Y, Sawyers CL, Scher HI. (2008). Targeting the androgen receptor pathway in prostate cancer. Curr Opin Pharmacol 8: 440-8
53. Chi Y, Huddleston MJ, Zhang X, et al. (2001). Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase. Genes Dev 15: 1078-92
54. Codina-Sola M, Rodriguez-Santiago B, Homs A, et al. (2015). Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders. Mol Autism 6: 21
55. Conaway RC, Conaway JW. (2011a). Function and regulation of the Mediator complex. Curr Opin Genet Dev 21: 225-30
56. Conaway RC, Conaway JW. (2011b). Origins and activity of the Mediator complex. Semin Cell Dev Biol 22: 729-34
57. Conaway RC, Conaway JW. (2013). The Mediator complex and transcription elongation. Biochim Biophys Acta 1829: 69-75
58. Cooper KF, Mallory MJ, Strich R. (1999). Oxidative stress-induced destruction of the yeast C-type cyclin Ume3p requires phosphatidylinositol-specific phospholipase C and the 26S proteasome. Mol Cell Biol 19: 3338-48
59. Core LJ, Lis JT. (2008). Transcription regulation through promoter-proximal pausing of RNA polymerase II. Science 319: 1791-2
60. Core LJ, Waterfall JJ, Lis JT. (2008). Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 322: 1845-8
61. Cosma MP, Panizza S, Nasmyth K. (2001). Cdk1 triggers association of RNA polymerase to cell cycle promoters only after recruitment of the mediator by SBF. Mol Cell 7: 1213-20
62. Cosma MP, Tanaka T, Nasmyth K. (1999). Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle- and developmentally regulated promoter. Cell 97: 299-311
63. Daniels DL, Ford M, Schwinn MK, et al. (2013). Mutual exclusivity of MED12/MED12L, MED13/13L, and CDK8/19 paralogs revealed within the CDK-Mediator kinase module. J Proteomics Bioinform S2: 004
64. Davidson BL, McCray PB Jr. (2011). Current prospects for RNA interference-based therapies. Nat Rev Genet 12: 329-40
65. Davis JA, Takagi Y, Kornberg RD, Asturias FA. (2002). Structure of the yeast RNA polymerase II holoenzyme: Mediator conformation and polymerase interaction. Mol Cell 10: 409-15
66. Davis MA, Larimore EA, Fissel BM, et al. (2013). The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator. Genes Dev 27: 151-6
67. de Graaff MA, Cleton-Jansen AM, Szuhai K, Bovee JV. (2013). Mediator complex subunit 12 exon 2 mutation analysis in different subtypes of smooth muscle tumors confirms genetic heterogeneity. Hum Pathol 44: 1597-604
68. de Lau W, Barker N, Clevers H. (2007). WNT signaling in the normal intestine and colorectal cancer. Front Biosci 12: 471-91
69. Di Tommaso S, Tinelli A, Malvasi A, Massari S. (2014). Missense mutations in exon 2 of the MED12 gene are involved in IGF-2 overexpression in uterine leiomyoma. Mol Hum Reprod 20: 1009-15
70. Ding N, Tomomori-Sato C, Sato S, et al. (2009). MED19 and MED26 are synergistic functional targets of the RE1 silencing transcription factor in epigenetic silencing of neuronal gene expression. J Biol Chem 284: 2648-56
71. Ding N, Zhou H, Esteve PO, et al. (2008). Mediator links epigenetic silencing of neuronal gene expression with x-linked mental retardation. Mol Cell 31: 347-59
72. Dominissini D, Moshitch-Moshkovitz S, Amariglio N, Rechavi G. (2011). Adenosin-to-inosine RNA editing meets cancer. Carcinogenesis 32: 1569-77
73. Donner AJ, Ebmeier CC, Taatjes DJ, Espinosa JM. (2010). CDK8 is a positive regulator of transcriptional elongation within the serum response network. Nat Struct Mol Biol 17: 194-201
74. Donner AJ, Hoover JM, Szostek SA, Espinosa JM. (2007a). Stimulus-specific transcriptional regulation within the p53 network. Cell Cycle 6: 2594-8
75. Donner AJ, Szostek S, Hoover JM, Espinosa JM. (2007b). CDK8 is a stimulus-specific positive coregulator of p53 target genes. Mol Cell 27: 121-33
76. Dowen JM, Fan ZP, Hnisz D, et al. (2014). Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes. Cell 159: 374-87
77. Dupont WD, Page DL, Parl FF, et al. (1994). Long-term risk of breast cancer in women with fibroadenoma. N Engl J Med 331: 10-15
78. Eaton KD, Martins RG. (2010). Maintenance chemotherapy in non-small cell lung cancer. J Natl Compr Cancer Netw 8: 815-21
79. Ebmeier CC, Taatjes DJ. (2010). Activator-Mediator binding regulates Mediator-cofactor interactions. Proc Natl Acad Sci USA 107: 11283-8
80. Eirew P, Steif A, Khattra J, et al. (2015). Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution. Nature 518: 422-6
81. Elmlund H, Baraznenok V, Lindahl M, et al. (2006). The cyclin-dependent kinase 8 module sterically blocks Mediator interactions with RNA polymerase II. Proc Natl Acad Sci USA 103: 15788-93
82. Endicott JA, Noble ME, Johnson LN. (2012). The structural basis for control of eukaryotic protein kinases. Annu Rev Biochem 81: 587-613
83. Ferlay J, Soerjomataram I, Dikshit R, et al. (2015). Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136: E359-86
84. Firestein R, Bass AJ, Kim SY, et al. (2008). CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity. Nature 455: 547-51
85. Firestein R, Shima K, Nosho K, et al. (2010). CDK8 expression in 470 colorectal cancers in relation to beta-catenin activation, other molecular alterations and patient survival. Int J Cancer 126: 2863-73
86. Fondell JD, Ge H, Roeder RG. (1996). Ligand induction of a transcriptionally active thyroid hormone receptor coactivator complex. Proc Natl Acad Sci USA 93: 8329-33
87. Foster ME, Garrahan N, Williams S. (1988). Fibroadenoma of the breast: a clinical and pathological study. J R Coll Surg Edinb 33: 16-19
88. Fryer CJ, White JB, Jones KA. (2004). Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell 16: 509-20
89. Fryns JP, Buttiens M. (1987). X-linked mental retardation with marfanoid habitus. Am J Med Genet 28: 267-74
90. Galamb O, Sipos F, Molnar B, et al. (2007). Evaluation of malignant and benign gastric biopsy specimens by mRNA expression profile and multivariate statistical methods. Cytometry B Clin Cytom 72: 299-309
91. Galbraith MD, Allen MA, Bensard CL, et al. (2013). HIF1A employs CDK8-mediator to stimulate RNAPII elongation in response to hypoxia. Cell 153: 1327-39
92. Galbraith MD, Donner AJ, Espinosa JM. (2010). CDK8: a positive regulator of transcription. Transcription 1: 4-12
93. Galbraith MD, Espinosa JM. (2011). Lessons on transcriptional control from the serum response network. Curr Opin Genet Dev 21: 160-6
94. Gao S, Alarcon C, Sapkota G, et al. (2009). Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling. Mol Cell 36: 457-68
95. Gill J, Ahluwalia MK, Geller D, Gorlick R. (2013). New targets and approaches in osteosarcoma. Pharmacol Ther 137: 89-99
96. Gobert V, Osman D, Bras S, et al. (2010). A genome-wide RNA interference screen identifies a differential role of the mediator CDK8 module subunits for GATA/RUNX-activated transcription in Drosophila. Mol Cell Biol 30: 2837-48
97. Grants JM, Goh GY, Taubert S. (2015). The Mediator complex of Caenorhabditis elegans: insights into the developmental and physiological roles of a conserved transcriptional coregulator. Nucleic Acids Res 43: 2442-53
98. Grasso CS, Wu YM, Robinson DR, et al. (2012). The mutational landscape of lethal castration-resistant prostate cancer. Nature 487: 239-43
99. Gu W, Malik S, Ito M, et al. (1999). A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation. Mol Cell 3: 97-108
100. Gu W, Wang C, Li W, et al. (2013). Tumor-suppressive effects of CDK8 in endometrial cancer cells. Cell Cycle 12: 987-99
101. Guenther MG, Levine SS, Boyer LA, et al. (2007). A chromatin landmark and transcription initiation at most promoters in human cells. Cell 130: 77-88
102. Guerzoni C, Amatori S, Giorgi L, et al. (2014). An aza-macrocycle containing maltolic side-arms (maltonis) as potential drug against human pediatric sarcomas. BMC Cancer 14: 137
103. Halder SK, Laknaur A, Miller J, et al. (2015). Novel MED12 gene somatic mutations in women from the Southern United States with symptomatic uterine fibroids. Mol Genet Genomics 290: 505-11
104. Hanahan D, Weinberg RA. (2011). Hallmarks of cancer: the next generation. Cell 144: 646-74
105. Hartwell LH. (2002). Nobel lecture. Yeast and cancer. Biosci Rep 22: 373-94
106. He L, Lu N, Dai Q, et al. (2013). Wogonin induced G1 cell cycle arrest by regulating Wnt/beta-catenin signaling pathway and inactivating CDK8 in human colorectal cancer carcinoma cells. Toxicology 312: 36-47
107. Heidegger I, Massoner P, Eder IE, et al. (2013). Novel therapeutic approaches for the treatment of castration-resistant prostate cancer. J Steroid Biochem Mol Biol 138: 248-56
108. Heinonen HR, Sarvilinna NS, Sjoberg J, et al. (2014). MED12 mutation frequency in unselected sporadic uterine leiomyomas. Fertil Steril 102: 1137-42
109. Hengartner CJ, Myer VE, Liao SM, et al. (1998). Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases. Mol Cell 2: 43-53
110. Hengartner CJ, Thompson CM, Zhang J, et al. (1995). Association of an activator with an RNA polymerase II holoenzyme. Genes Dev 9: 897-910
111. Hirst M, Kobor MS, Kuriakose N, et al. (1999). GAL4 is regulated by the RNA polymerase II holoenzyme-associated cyclin-dependent protein kinase SRB10/CDK8. Mol Cell 3: 673-8
112. Hnisz D, Abraham BJ, Lee TI, et al. (2013). Super-enhancers in the control of cell identity and disease. Cell 155: 934-47
113. Ho AS, Kannan K, Roy DM, et al. (2013). The mutational landscape of adenoid cystic carcinoma. Nat Genet 45: 791-8
114. Hodis E, Watson IR, Kryukov GV, et al. (2012). A landscape of driver mutations in melanoma. Cell 150: 251-63
115. Hoeppner S, Baumli S, Cramer P. (2005). Structure of the mediator subunit cyclin C and its implications for CDK8 function. J Mol Biol 350: 833-42
116. Holstege FC, Jennings EG, Wyrick JJ, et al. (1998). Dissecting the regulatory circuitry of a eukaryotic genome. Cell 95: 717-28
117. Hong SK, Dawid IB. (2011). The transcriptional mediator component Med12 is required for hindbrain boundary formation. PLoS One 6: e19076
118. Huang S, Holzel M, Knijnenburg T, et al. (2012). MED12 controls the response to multiple cancer drugs through regulation of TGF-beta receptor signaling. Cell 151: 937-50
119. Hunt T, Nasmyth K, Novak B. (2011). The cell cycle. Philos Trans R Soc Lond B Biol Sci 366: 3494-7
120. Huse M, Kuriyan J. (2002). The conformational plasticity of protein kinases. Cell 109: 275-82
121. Imielinski M, Berger AH, Hammerman PS, et al. (2012). Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 150: 1107-20
122. Inuzuka H, Gao D, Finley LW, et al. (2012). Acetylation-dependent regulation of Skp2 function. Cell 150: 179-93
123. Ito M, Yuan CX, Malik S, et al. (1999). Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators. Mol Cell 3: 361-70
124. Iyer G, Al-Ahmadie H, Schultz N, et al. (2013). Prevalence and co-occurrence of actionable genomic alterations in high-grade bladder cancer. J Clin Oncol 31: 3133-40
125. Janody F, Martirosyan Z, Benlali A, Treisman JE. (2003). Two subunits of the Drosophila mediator complex act together to control cell affinity. Development 130: 3691-701
126. Janody F, Treisman JE. (2011). Requirements for mediator complex subunits distinguish three classes of notch target genes at the Drosophila wing margin. Dev Dyn 240: 2051-9
127. Je EM, Kim MR, Min KO, et al. (2012). Mutational analysis of MED12 exon 2 in uterine leiomyoma and other common tumors. Int J Cancer 131: E1044-7
128. Jerant AF, Johnson JT, Sheridan CD, Caffrey TJ. (2000). Early detection and treatment of skin cancer. Am Fam Physician 62: 357-68,. 375-6, 381-2
129. Jiang BH, Rue E, Wang GL, et al. (1996). Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J Biol Chem 271: 17771-8
130. Jiao Y, Pawlik TM, Anders RA, et al. (2013). Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nat Genet 45: 1470-3
131. Jin C, Strich R, Cooper KF. (2014). Slt2p phosphorylation induces cyclin C nuclear-to-cytoplasmic translocation in response to oxidative stress. Mol Biol Cell 25: 1396-407
132. Joensuu T, Hamalainen R, Yuan B, et al. (2001). Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3. Am J Hum Genet 69: 673-84
133. Johnson A, Skotheim JM. (2013). Start and the restriction point. Curr Opin Cell Biol 25: 717-23
134. Johnston JJ, Sapp JC, Turner JT, et al. (2010). Molecular analysis expands the spectrum of phenotypes associated with GLI3 mutations. Hum Mutat 31: 1142-54
135. Kaelin WG, Jr, Ratcliffe PJ. (2008). Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 30: 393-402
136. Kagey MH, Newman JJ, Bilodeau S, et al. (2010). Mediator and cohesin connect gene expression and chromatin architecture. Nature 467: 430-5
137. Kakiuchi M, Nishizawa T, Ueda H, et al. (2014). Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma. Nat Genet 46: 583-7
138. Kampjarvi K, Jarvinen TM, Heikkinen T, et al. (2015). Somatic MED12 mutations are associated with poor prognosis markers in chronic lymphocytic leukemia. Oncotarget 6: 1884-8
139. Kampjarvi K, Makinen N, Kilpivaara O, et al. (2012). Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer. Br J Cancer 107: 1761-5
140. Kampjarvi K, Park MJ, Mehine M, et al. (2014). Mutations in Exon 1 highlight the role of MED12 in uterine leiomyomas. Hum Mutat 35: 1136-41
141. Kapoor A, Goldberg MS, Cumberland LK, et al. (2010). The histone variant macroH2A suppresses melanoma progression through regulation of CDK8. Nature 468: 1105-9
142. Karantanos T, Corn PG, Thompson TC. (2013). Prostate cancer progression after androgen deprivation therapy: mechanisms of castrate resistance and novel therapeutic approaches. Oncogene 32: 5501-11
143. Kaur M, Velmurugan B, Tyagi A, et al. (2010). Silibinin suppresses growth of human colorectal carcinoma SW480 cells in culture and xenograft through down-regulation of beta-catenin-dependent signaling. Neoplasia 12: 415-24
144. Keightley MC, Layton JE, Hayman JW, et al. (2011). Mediator subunit 12 is required for neutrophil development in zebrafish. PLoS One 6: e23845
145. Kim DH, Rossi JJ. (2007). Strategies for silencing human disease using RNA interference. Nat Rev Genet 8: 173-84
146. Kim MY, Han SI, Lim SC. (2011). Roles of cyclin-dependent kinase 8 and beta-catenin in the oncogenesis and progression of gastric adenocarcinoma. Int J Oncol 38: 1375-83
147. Kim PH, Cha EK, Sfakianos JP, et al. (2015). Genomic predictors of survival in patients with high-grade urothelial carcinoma of the bladder. Eur Urol 67: 198-201
148. Kim S, Xu X, Hecht A, Boyer TG. (2006). Mediator is a transducer of Wnt/beta-catenin signaling. J Biol Chem 281: 14066-75
149. Kim YJ, Bjorklund S, Li Y, et al. (1994). A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II. Cell 77: 599-608
150. Kim YW, Park J, Lee HJ, et al. (2012). TGF-beta sensitivity is determined by N-linked glycosylation of the type II TGF-beta receptor. Biochem J 445: 403-11
151. Kinzler KW, Vogelstein B. (1998). Landscaping the cancer terrain. Science 280: 1036-7
152. Kishi T, Ikeda A, Koyama N, et al. (2008). A refined two-hybrid system reveals that SCF(Cdc4)-dependent degradation of Swi5 contributes to the regulatory mechanism of S-phase entry. Proc Natl Acad Sci USA 105: 14497-502
153. Knuesel MT, Meyer KD, Bernecky C, Taatjes DJ. (2009a). The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function. Genes Dev 23: 439-51
154. Knuesel MT, Meyer KD, Donner AJ, et al. (2009b). The human CDK8 subcomplex is a histone kinase that requires Med12 for activity and can function independently of mediator. Mol Cell Biol 29: 650-61
155. Knuesel MT, Taatjes DJ. (2011). Mediator and post-recruitment regulation of RNA polymerase II. Transcription 2: 28-31
156. Koleske AJ, Young RA. (1994). An RNA polymerase II holoenzyme responsive to activators. Nature 368: 466-9
157. Kornberg RD. (2005). Mediator and the mechanism of transcriptional activation. Trends Biochem Sci 30: 235-9
158. Kretzschmar M, Stelzer G, Roeder RG, Meisterernst M. (1994). RNA polymerase II cofactor PC2 facilitates activation of transcription by GAL4-AH in vitro. Mol Cell Biol 14: 3927-37
159. Kuchin S, Yeghiayan P, Carlson M. (1995). Cyclin-dependent protein kinase and cyclin homologs SSN3 and SSN8 contribute to transcriptional control in yeast. Proc Natl Acad Sci USA 92: 4006-10
160. Lai F, Orom UA, Cesaroni M, et al. (2013). Activating RNAs associate with Mediator to enhance chromatin architecture and transcription. Nature 494: 497-501
161. Lariviere L, Plaschka C, Seizl M, et al. (2012). Structure of the Mediator head module. Nature 492: 448-51
162. Lawrence MS, Stojanov P, Mermel CH, et al. (2014). Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505: 495-501
163. Lee W, Teckie S, Wiesner T, et al. (2014). PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors. Nat Genet 46: 1227-32
164. Lehner B, Crombie C, Tischler J, et al. (2006). Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways. Nat Genet 38: 896-903
165. Levy DE, Darnell JE Jr. (2002). Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol 3: 651-62
166. Lewis BA, Reinberg D. (2003). The mediator coactivator complex: functional and physical roles in transcriptional regulation. J Cell Sci 116: 3667-75
167. Li H, Lahti JM, Valentine M, et al. (1996). Molecular cloning and chromosomal localization of the human cyclin C (CCNC) and cyclin E (CCNE) genes: deletion of the CCNC gene in human tumors. Genomics 32: 253-9
168. Li J, Li X, Kong X, et al. (2014a). MiRNA-26b inhibits cellular proliferation by targeting CDK8 in breast cancer. Int J Clin Exp Med 7: 558-65
169. Li N, Fassl A, Chick J, et al. (2014b). Cyclin C is a haploinsufficient tumour suppressor. Nat Cell Biol 16: 1080-91
170. Li XY, Luo QF, Wei CK, et al. (2014c). MiRNA-107 inhibits proliferation and migration by targeting CDK8 in breast cancer. Int J Clin Exp Med 7: 32-40
171. Liao SM, Zhang J, Jeffery DA, et al. (1995). A kinase-cyclin pair in the RNA polymerase II holoenzyme. Nature 374: 193-6
172. Lim WK, Ong CK, Tan J, et al. (2014). Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma. Nat Genet 46: 877-80
173. Lin DC, Meng X, Hazawa M, et al. (2014). The genomic landscape of nasopharyngeal carcinoma. Nat Genet 46: 866-71
174. Lin HK, Chen Z, Wang G, et al. (2010). Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. Nature 464: 374-9
175. Lin X, Rinaldo L, Fazly AF, Xu X. (2007). Depletion of Med10 enhances Wnt and suppresses Nodal signaling during zebrafish embryogenesis. Dev Biol 303: 536-48
176. Liu Y, Kung C, Fishburn J, et al. (2004). Two cyclin-dependent kinases promote RNA polymerase II transcription and formation of the scaffold complex. Mol Cell Biol 24: 1721-35
177. Liu Y, Ranish JA, Aebersold R, Hahn S. (2001). Yeast nuclear extract contains two major forms of RNA polymerase II mediator complexes. J Biol Chem 276: 7169-75
178. Loenarz C, Coleman ML, Boleininger A, et al. (2011). The hypoxia-inducible transcription factor pathway regulates oxygen sensing in the simplest animal, Trichoplax adhaerens. EMBO Rep 12: 63-70
179. Lu S, Lee J, Revelo M, et al. (2007). Smad3 is overexpressed in advanced human prostate cancer and necessary for progressive growth of prostate cancer cells in nude mice. Clin Cancer Res 13: 5692-702
180. Ludwig JA, Weinstein JN. (2005). Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer 5: 845-56
181. Lujan JE, Carlin ME, Lubs HA. (1984). A form of X-linked mental retardation with marfanoid habitus. Am J Med Genet 17: 311-22
182. Lupien M, Brown M. (2009). Cistromics of hormone-dependent cancer. Endocr Relat Cancer 16: 381-9
183. MacDonald BT, Tamai K, He X. (2009). Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17: 9-26
184. Majewski IJ, Kluijt I, Cats A, et al. (2013). An alpha-E-catenin (CTNNA1) mutation in hereditary diffuse gastric cancer. J Pathol 229: 621-9
185. Makinen N, Heinonen HR, Moore S, et al. (2011a). MED12 exon 2 mutations are common in uterine leiomyomas from South African patients. Oncotarget 2: 966-9
186. Makinen N, Mehine M, Tolvanen J, et al. (2011b). MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science 334: 252-5
187. Makinen N, Vahteristo P, Kampjarvi K, et al. (2013). MED12 exon 2 mutations in histopathological uterine leiomyoma variants. Eur J Hum Genet 21: 1300-3
188. Malik S, Gu W, Wu W, et al. (2000). The USA-derived transcriptional coactivator PC2 is a submodule of TRAP/SMCC and acts synergistically with other PCs. Mol Cell 5: 753-60
189. Malik S, Roeder RG. (2010). The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation. Nat Rev Genet 11: 761-72
190. Malumbres M, Harlow E, Hunt T, et al. (2009). Cyclin-dependent kinases: a family portrait. Nat Cell Biol 11: 1275-6
191. Manning G, Whyte DB, Martinez R, et al. (2002). The protein kinase complement of the human genome. Science 298: 1912-34
192. Marguerat S, Jensen TS, de Lichtenberg U, et al. (2006). The more the merrier: comparative analysis of microarray studies on cell cycle-regulated genes in fission yeast. Yeast 23: 261-77
193. Markowski DN, Bartnitzke S, Loning T, et al. (2012). MED12 mutations in uterine fibroids-their relationship to cytogenetic subgroups. Int J Cancer 131: 1528-36
194. Markowski DN, Huhle S, Nimzyk R, et al. (2013). MED12 mutations occurring in benign and malignant mammalian smooth muscle tumors. Genes Chromosomes Cancer 52: 297-304
195. Martin ES, Tonon G, Sinha R, et al. (2007). Common and distinct genomic events in sporadic colorectal cancer and diverse cancer types. Cancer Res 67: 10736-43
196. Matsubara A, Sekine S, Yoshida M, et al. (2013). Prevalence of MED12 mutations in uterine and extrauterine smooth muscle tumours. Histopathology 62: 657-61
197. Mayeux R. (2004). Biomarkers: potential uses and limitations. NeuroRx 1: 182-8
198. McGuire MM, Yatsenko A, Hoffner L, et al. (2012). Whole exome sequencing in a random sample of North American women with leiomyomas identifies MED12 mutations in majority of uterine leiomyomas. PLoS One 7: e33251
199. Mehine M, Kaasinen E, Makinen N, et al. (2013). Characterization of uterine leiomyomas by whole-genome sequencing. N Engl J Med 369: 43-53
200. Meyer KD, Lin SC, Bernecky C, et al. (2010). p53 activates transcription by directing structural shifts in Mediator. Nat Struct Mol Biol 17: 753-60
201. Mo X, Kowenz-Leutz E, Xu H, Leutz A. (2004). Ras induces mediator complex exchange on C/EBP beta. Mol Cell 13: 241-50
202. Moghal N, Sternberg PW. (2003). A component of the transcriptional mediator complex inhibits RAS-dependent vulval fate specification in C elegans. Development 130: 57-69
203. Monni O, Barlund M, Mousses S, et al. (2001). Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer. Proc Natl Acad Sci USA 98: 5711-16
204. Moravek MB, Yin P, Ono M, et al. (2015). Ovarian steroids, stem cells and uterine leiomyoma: therapeutic implications. Hum Reprod Update 21: 1-12
205. Morris EJ, Ji JY, Yang F, et al. (2008). E2F1 represses beta-catenin transcription and is antagonized by both pRB and CDK8. Nature 455: 552-6
206. Mukhopadhyay A, Kramer JM, Merkx G, et al. (2010). CDK19 is disrupted in a female patient with bilateral congenital retinal folds, microcephaly and mild mental retardation. Hum Genet 128: 281-91
207. Muncke N, Jung C, Rudiger H, et al. (2003). Missense mutations and gene interruption in PROSIT240, a novel TRAP240-like gene, in patients with congenital heart defect (transposition of the great arteries). Circulation 108: 2843-50
208. Muto A, Ikeda S, Lopez-Burks ME, et al. (2014). Nipbl and mediator cooperatively regulate gene expression to control limb development. PLoS Genet 10: e1004671
209. Myer VE, Young RA. (1998). RNA polymerase II holoenzymes and subcomplexes. J Biol Chem 273: 27757-60
210. Myers LC, Gustafsson CM, Bushnell DA, et al. (1998). The Med proteins of yeast and their function through the RNA polymerase II carboxy-terminal domain. Genes Dev 12: 45-54
211. Myers LC, Kornberg RD. (2000). Mediator of transcriptional regulation. Annu Rev Biochem 69: 729-49
212. Naar AM, Beaurang PA, Zhou S, et al. (1999). Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature 398: 828-32
213. Naar AM, Taatjes DJ, Zhai W, et al. (2002). Human CRSP interacts with RNA polymerase II CTD and adopts a specific CTD-bound conformation. Genes Dev 16: 1339-44 et al. [Epub ahead of print]. doi: 10.1002/cam4.462
214. Nagasawa S, Maeda I, Fukuda T, et al. (2015). MED12 exon 2 mutations in phyllodes tumors of the breast. Cancer Med. [Epub ahead of print]. doi: 10.1002/cam4.462
215. Nakayama K, Nagahama H, Minamishima YA, et al. (2004). Skp2-mediated degradation of p27 regulates progression into mitosis. Dev Cell 6: 661-72
216. Nelson C, Goto S, Lund K, et al. (2003). Srb10/Cdk8 regulates yeast filamentous growth by phosphorylating the transcription factor Ste12. Nature 421: 187-90
217. Nemet J, Jelicic B, Rubelj I, Sopta M. (2014). The two faces of Cdk8, a positive/negative regulator of transcription. Biochimie 97: 22-7
218. Newman JJ, Young RA. (2010). Connecting transcriptional control to chromosome structure and human disease. Cold Spring Harb Symp Quant Biol 75: 227-35
219. Niehrs C, Acebron SP. (2012). Mitotic and mitogenic Wnt signalling. EMBO J 31: 2705-13
220. Nolen B, Taylor S, Ghosh G. (2004). Regulation of protein kinases; controlling activity through activation segment conformation. Mol Cell 15: 661-75
221. Nonet ML, Young RA. (1989). Intragenic and extragenic suppressors of mutations in the heptapeptide repeat domain of Saccharomyces cerevisiae RNA polymerase II. Genetics 123: 715-24
222. Nurse P, Masui Y, Hartwell L. (1998). Understanding the cell cycle. Nat Med 4: 1103-6
223. Ohata N, Ito S, Yoshida A, et al. (2006). Highly frequent allelic loss of chromosome 6q16-23 in osteosarcoma: involvement of cyclin C in osteosarcoma. Int J Mol Med 18: 1153-8
224. Oliva A, Rosebrock A, Ferrezuelo F, et al. (2005). The cell cycle-regulated genes of Schizosaccharomyces pombe. PLoS Biol 3: e225
225. Onken MD, Winkler AE, Kanchi KL, et al. (2014). A surprising cross-species conservation in the genomic landscape of mouse and human oral cancer identifies a transcriptional signature predicting metastatic disease. Clin Cancer Res 20: 2873-84
226. Ono M, Qiang W, Serna VA, et al. (2012). Role of stem cells in human uterine leiomyoma growth. PLoS One 7: e36935
227. Ono M, Yin P, Navarro A, et al. (2013). Paracrine activation of WNT/beta-catenin pathway in uterine leiomyoma stem cells promotes tumor growth. Proc Natl Acad Sci USA 110: 17053-8
228. Opitz JM, Smith JF, Santoro L. (2008). The FG syndromes (Online Mendelian Inheritance in Man 305450): perspective in 2008. Adv Pediatr 55: 123-70
229. Paoletti AC, Parmely TJ, Tomomori-Sato C, et al. (2006). Quantitative proteomic analysis of distinct mammalian Mediator complexes using normalized spectral abundance factors. Proc Natl Acad Sci USA 103: 18928-33
230. Pavri R, Lewis B, Kim TK, et al. (2005). PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator. Mol Cell 18: 83-96
231. Paz N, Levanon EY, Amariglio N, et al. (2007). Altered adenosine-to-inosine RNA editing in human cancer. Genome Res 17: 1586-95
232. Peifer M, Fernandez-Cuesta L, Sos ML, et al. (2012). Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet 44: 1104-10
233. Peng X, Karuturi RK, Miller LD, et al. (2005). Identification of cell cycle-regulated genes in fission yeast. Mol Biol Cell 16: 1026-42
234. Perot G, Croce S, Ribeiro A, et al. (2012). MED12 alterations in both human benign and malignant uterine soft tissue tumors. PLoS One 7: e40015
235. Phillips-Cremins JE, Sauria ME, Sanyal A, et al. (2013). Architectural protein subclasses shape 3D organization of genomes during lineage commitment. Cell 153: 1281-95 [Epub ahead of print]. doi: 10.1111/his.12712
236. Piscuoglio S, Murray M, Fusco N, et al. (2015). MED12 somatic mutations in fibroadenomas and phyllodes tumors of the breast. Histopathology. [Epub ahead of print]. doi: 10.1111/his.12712
237. Plaschka C, Lariviere L, Wenzeck L, et al. (2015). Architecture of the RNA polymerase II-Mediator core initiation complex. Nature 518: 376-80
238. Porter DC, Farmaki E, Altilia S, et al. (2012). Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities. Proc Natl Acad Sci USA 109: 13799-804
239. Poss ZC, Ebmeier CC, Taatjes DJ. (2013). The Mediator complex and transcription regulation. Crit Rev Biochem Mol Biol 48: 575-608
240. Poste G. (2011). Bring on the biomarkers. Nature 469: 156-7
241. Prenzel T, Kramer F, Bedi U, et al. (2012). Cohesin is required for expression of the estrogen receptor-alpha (ESR1) gene. Epigenetics Chromatin 5: 13
242. Rachez C, Lemon BD, Suldan Z, et al. (1999). Ligand-dependent transcription activation by nuclear receptors requires the DRIP complex. Nature 398: 824-8
243. Rahl PB, Lin CY, Seila AC, et al. (2010). c-Myc regulates transcriptional pause release. Cell 141: 432-45
244. Rajender PS, Vasavi M, Vuruputuri U. (2011). Identification of novel selective antagonists for cyclin C by homology modeling and virtual screening. Int J Biol Macromol 48: 292-300
245. Rau MJ, Fischer S, Neumann CJ. (2006). Zebrafish Trap230/Med12 is required as a coactivator for Sox9-dependent neural crest, cartilage and ear development. Dev Biol 296: 83-93
246. Ravegnini G, Marino-Enriquez A, Slater J, et al. (2013). MED12 mutations in leiomyosarcoma and extrauterine leiomyoma. Mod Pathol 26: 743-9
247. Reinfuss M, Mitus J, Duda K, et al. (1996). The treatment and prognosis of patients with phyllodes tumor of the breast: an analysis of 170 cases. Cancer 77: 910-16
248. Reinhardt HC, Schumacher B. (2012). The p53 network: cellular and systemic DNA damage responses in aging and cancer. Trends Genet 28: 128-36
249. Risheg H, Graham JM Jr, Clark RD, et al. (2007). A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome. Nat Genet 39: 451-3
250. Robinson G, Parker M, Kranenburg TA, et al. (2012a). Novel mutations target distinct subgroups of medulloblastoma. Nature 488: 43-8
251. Robinson PJ, Bushnell DA, Trnka MJ, et al. (2012b). Structure of the mediator head module bound to the carboxy-terminal domain of RNA polymerase II. Proc Natl Acad Sci USA 109: 17931-5
252. Rocha PP, Scholze M, Bleiss W, Schrewe H. (2010). Med12 is essential for early mouse development and for canonical Wnt and Wnt/PCP signaling. Development 137: 2723-31
253. Roti G, Stegmaier K. (2014). New approaches to target T-ALL. Front Oncol 4: 170
254. Rudin CM, Durinck S, Stawiski EW, et al. (2012). Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat Genet 44: 1111-16
255. Rustici G, Mata J, Kivinen K, et al. (2004). Periodic gene expression program of the fission yeast cell cycle. Nat Genet 36: 809-17
256. Ryu S, Zhou S, Ladurner AG, Tjian R. (1999). The transcriptional cofactor complex CRSP is required for activity of the enhancer-binding protein Sp1. Nature 397: 446-50
257. Sadzak I, Schiff M, Gattermeier I, et al. (2008). Recruitment of Stat1 to chromatin is required for interferon-induced serine phosphorylation of Stat1 transactivation domain. Proc Natl Acad Sci USA 105: 8944-9
258. Sato S, Tomomori-Sato C, Parmely TJ, et al. (2004). A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology. Mol Cell 14: 685-91
259. Schneider EV, Bottcher J, Blaesse M, et al. (2011). The structure of CDK8/CycC implicates specificity in the CDK/cyclin family and reveals interaction with a deep pocket binder. J Mol Biol 412: 251-66
260. Schneider EV, Bottcher J, Huber R, et al. (2013). Structure-kinetic relationship study of CDK8/CycC specific compounds. Proc Natl Acad Sci USA 110: 8081-6
261. Schoenborn JR, Wilson CB. (2007). Regulation of interferon-gamma during innate and adaptive immune responses. Adv Immunol 96: 41-101
262. Schwartz CE, Tarpey PS, Lubs HA, et al. (2007). The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene. J Med Genet 44: 472-7
263. Schwetye KE, Pfeifer JD, Duncavage EJ. (2014). MED12 exon 2 mutations in uterine and extrauterine smooth muscle tumors. Hum Pathol 45: 65-70
264. Semenza GL. (2014). Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annu Rev Pathol 9: 47-71
265. Seo JO, Han SI, Lim SC. (2010). Role of CDK8 and beta-catenin in colorectal adenocarcinoma. Oncol Rep 24: 285-91
266. Seshagiri S, Stawiski EW, Durinck S, et al. (2012). Recurrent R-spondin fusions in colon cancer. Nature 488: 660-4
267. Shah SP, Roth A, Goya R, et al. (2012). The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature 486: 395-9
268. Shaikhibrahim Z, Offermann A, Braun M, et al. (2014). MED12 overexpression is a frequent event in castration-resistant prostate cancer. Endocr Relat Cancer 21: 663-75
269. Shi Y, Massague J. (2003). Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113: 685-700
270. Shin CH, Chung WS, Hong SK, et al. (2008). Multiple roles for Med12 in vertebrate endoderm development. Dev Biol 317: 467-79
271. Slotkin W, Nishikura K. (2013). Adenosine-to-inosine RNA editing and human disease. Genome Med 5: 105
272. Smalley KS, Flaherty KT. (2009). Development of a novel chemical class of BRAF inhibitors offers new hope for melanoma treatment. Future Oncol 5: 775-8
273. Song W, Treich I, Qian N, Kuchin S, Carlson M. (1996). SSN genes that affect transcriptional repression in Saccharomyces cerevisiae encode SIN4, ROX3, and SRB proteins associated with RNA polymerase II. Mol Cell Biol 16: 115-20
274. Song YQ, Ma XH, Ma GL, et al. (2014). MicroRNA-107 promotes proliferation of gastric cancer cells by targeting cyclin dependent kinase 8. Diagn Pathol 9: 164
275. Spaeth JM, Kim NH, Boyer TG. (2011). Mediator and human disease. Semin Cell Dev Biol 22: 776-87
276. Spahr H, Khorosjutina O, Baraznenok V, et al. (2003). Mediator influences Schizosaccharomyces pombe RNA polymerase II-dependent transcription in vitro. J Biol Chem 278: 51301-6
277. Spellman PT, Sherlock G, Zhang MQ, et al. (1998). Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 9: 3273-97
278. Staab J, Herrmann-Lingen C, Meyer T. (2013). CDK8 as the STAT1 serine 727 kinase? JAKSTAT 2: e24275
279. Stark GR, Darnell JE Jr. (2012). The JAK-STAT pathway at twenty. Immunity 36: 503-14
280. Stephens PJ, Tarpey PS, Davies H, et al. (2012). The landscape of cancer genes and mutational processes in breast cancer. Nature 486: 400-4
281. Stewart EA. (2001). Uterine fibroids. Lancet 357: 293-8
282. Stransky N, Egloff AM, Tward AD, et al. (2011). The mutational landscape of head and neck squamous cell carcinoma. Science 333: 1157-60
283. Struhl K. (2005). Transcriptional activation: mediator can act after preinitiation complex formation. Mol Cell 17: 752-4
284. Sun X, Zhang Y, Cho H, et al. (1998). NAT, a human complex containing Srb polypeptides that functions as a negative regulator of activated transcription. Mol Cell 2: 213-22
285. Szilagyi Z, Banyai G, Lopez MD, et al. (2012). Cyclin-dependent kinase 8 regulates mitotic commitment in fission yeast. Mol Cell Biol 32: 2099-109
286. Taatjes DJ, Naar AM, Andel F III, et al. (2002). Structure, function, and activator-induced conformations of the CRSP coactivator. Science 295: 1058-62
287. Takahashi H, Parmely TJ, Sato S, et al. (2011). Human mediator subunit MED26 functions as a docking site for transcription elongation factors. Cell 146: 92-104
288. Talluri S, Dick FA. (2012). Regulation of transcription and chromatin structure by pRB: here, there and everywhere. Cell Cycle 11: 3189-98
289. Tan PH, Ellis IO. (2013). Myoepithelial and epithelial-myoepithelial, mesenchymal and fibroepithelial breast lesions: updates from the WHO Classification of Tumours of the Breast 2012. J Clin Pathol 66: 465-70
290. Taylor BS, Schultz N, Hieronymus H, et al. (2010). Integrative genomic profiling of human prostate cancer. Cancer Cell 18: 11-22
291. Tebb G, Moll T, Dowzer C, Nasmyth K. (1993). SWI5 instability may be necessary but is not sufficient for asymmetric HO expression in yeast. Genes Dev 7: 517-28
292. Thiery JP. (2009). Epithelial-mesenchymal transitions in cancer onset and progression. Bull Acad Natl Med 193: 1969-78; discussion 1978-9
293. Treisman J. (2001). Drosophila homologues of the transcriptional coactivation complex subunits TRAP240 and TRAP230 are required for identical processes in eye-antennal disc development. Development 128: 603-15
294. Tsafrir D, Bacolod M, Selvanayagam Z, et al. (2006). Relationship of gene expression and chromosomal abnormalities in colorectal cancer. Cancer Res 66: 2129-37
295. Tsai KL, Sato S, Tomomori-Sato C, et al. (2013). A conserved Mediator-CDK8 kinase module association regulates Mediator-RNA polymerase II interaction. Nat Struct Mol Biol 20: 611-19
296. Tsai KL, Tomomori-Sato C, Sato S, et al. (2014). Subunit architecture and functional modular rearrangements of the transcriptional mediator complex. Cell 157: 1430-44
297. Tsutsui T, Fukasawa R, Shinmyouzu K, et al. (2013). Mediator complex recruits epigenetic regulators via its two cyclin-dependent kinase subunits to repress transcription of immune response genes. J Biol Chem 288: 20955-65
298. Tsutsui T, Fukasawa R, Tanaka A, et al. (2011). Identification of target genes for the CDK subunits of the Mediator complex. Genes Cells 16: 1208-18
299. Tsutsui T, Umemura H, Tanaka A, et al. (2008). Human mediator kinase subunit CDK11 plays a negative role in viral activator VP16-dependent transcriptional regulation. Genes Cells 13: 817-26
300. Turunen M, Spaeth JM, Keskitalo S, et al. (2014). Uterine leiomyoma-linked MED12 mutations disrupt mediator-associated CDK activity. Cell Rep 7: 654-60
301. Utami KH, Winata CL, Hillmer AM, et al. (2014). Impaired development of neural-crest cell-derived organs and intellectual disability caused by MED13L haploinsufficiency. Hum Mutat 35: 1311-20
302. van Haelst MM, Monroe GR, Duran K, et al. (2015). Further confirmation of the MED13L haploinsufficiency syndrome. Eur J Hum Genet 23: 135-8
303. Verlinden L, Verstuyf A, Van Camp M, et al. (2000). Two novel 14-Epi-analogues of 1,25-dihydroxyvitamin D3 inhibit the growth of human breast cancer cells in vitro and in vivo. Cancer Res 60: 2673-9
304. Vogelstein B, Papadopoulos N, Velculescu VE, et al. (2013). Cancer genome landscapes. Science 339: 1546-58
305. Vogl MR, Reiprich S, Kuspert M, et al. (2013). Sox10 cooperates with the mediator subunit 12 during terminal differentiation of myelinating glia. J Neurosci 33: 6679-90
306. Vulto-van Silfhout AT, de Vries BB, van Bon BW, et al. (2013). Mutations in MED12 cause X-linked Ohdo syndrome. Am J Hum Genet 92: 401-6
307. Walker CL, Stewart EA. (2005). Uterine fibroids: the elephant in the room. Science 308: 1589-92
308. Wang G, Cantin GT, Stevens JL, Berk AJ. (2001). Characterization of mediator complexes from HeLa cell nuclear extract. Mol Cell Biol 21: 4604-13
309. Wang K, Kan J, Yuen ST, et al. (2011). Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nat Genet 43: 1219-23
310. Wang K, Yuen ST, Xu J, et al. (2014a). Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet 46: 573-82
311. Wang X, Sun Q, Ding Z, et al. (2014b). Redefining the modular organization of the core Mediator complex. Cell Res 24: 796-808
312. Wang X, Wang J, Ding Z, et al. (2013). Structural flexibility and functional interaction of Mediator Cdk8 module. Protein Cell 4: 911-20
313. Wang X, Yang N, Uno E, et al. (2006). A subunit of the mediator complex regulates vertebrate neuronal development. Proc Natl Acad Sci USA 103: 17284-9
314. Weinstock MA. (2001). Epidemiology, etiology, and control of melanoma. Med Health R I 84: 234-6
315. Wen Z, Zhong Z, Darnell JE Jr. (1995). Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell 82: 241-50
316. Weng AP, Ferrando AA, Lee W, et al. (2004). Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306: 269-71
317. Werner HM, Salvesen HB. (2014). Current status of molecular biomarkers in endometrial cancer. Curr Oncol Rep 16: 403
318. Westerling T, Kuuluvainen E, Makela TP. (2007). Cdk8 is essential for preimplantation mouse development. Mol Cell Biol 27: 6177-82
319. Whitfield ML, Sherlock G, Saldanha AJ, et al. (2002). Identification of genes periodically expressed in the human cell cycle and their expression in tumors. Mol Biol Cell 13: 1977-2000
320. Whyte WA, Orlando DA, Hnisz D, et al. (2013). Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 153: 307-19
321. Wilhelm SM, Adnane L, Newell P, et al. (2008). Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling. Mol Cancer Ther 7: 3129-40
322. Wu SY, de Borsetti NH, Bain EJ, et al. (2014). Mediator subunit 12 coordinates intrinsic and extrinsic control of epithalamic development. Dev Biol 385: 13-22
323. Xu D, Li CF, Zhang X, et al. (2015). Skp2-MacroH2A1-CDK8 axis orchestrates G2/M transition and tumorigenesis. Nat Commun 6: 6641
324. Xu W, Amire-Brahimi B, Xie XJ, et al. (2014). All-atomic molecular dynamic studies of human CDK8: insight into the A-loop, point mutations and binding with its partner CycC. Comput Biol Chem 51: 1-11
325. Xu W, Ji JY. (2011). Dysregulation of CDK8 and Cyclin C in tumorigenesis. J Genet Genomics 38: 439-52
326. Xu X, Zhou H, Boyer TG. (2011). Mediator is a transducer of amyloid-precursor-protein-dependent nuclear signalling. EMBO Rep 12: 216-22
327. Yamamoto S, Schulze KL, Bellen HJ. (2014). Introduction to Notch signaling. Methods Mol Biol 1187: 1-14
328. Yang HP, Wentzensen N, Trabert B, et al. (2013). Endometrial cancer risk factors by 2 main histologic subtypes: the NIH-AARP Diet and Health Study. Am J Epidemiol 177: 142-51
329. Yang J, Huang J, Dasgupta M, et al. (2010). Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes. Proc Natl Acad Sci USA 107: 21499-504
330. Yang X, Kandil D, Cosar EF, Khan A. (2014). Fibroepithelial tumors of the breast: pathologic and immunohistochemical features and molecular mechanisms. Arch Pathol Lab Med 138: 25-36
331. Yin JW, Wang G. (2014). The Mediator complex: a master coordinator of transcription and cell lineage development. Development 141: 977-87
332. Yin P, Ono M, Moravek MB, et al. (2015). Human uterine leiomyoma stem/progenitor cells expressing CD34 and CD49b initiate tumors in vivo. J Clin Endocrinol Metab 100: E601-6
333. Yoda A, Kouike H, Okano H, Sawa H. (2005). Components of the transcriptional Mediator complex are required for asymmetric cell division in C elegans. Development 132: 1885-93
334. Yoshida M, Sekine S, Ogawa R, et al. (2015). Frequent MED12 mutations in phyllodes tumours of the breast. Br J Cancer 112: 1703-8
335. Yuan X, Cai C, Chen S, et al. (2014). Androgen receptor functions in castration-resistant prostate cancer and mechanisms of resistance to new agents targeting the androgen axis. Oncogene 33: 2815-25
336. Zhang Q, Ubago J, Li L, et al. (2014a). Molecular analyses of 6 different types of uterine smooth muscle tumors: emphasis in atypical leiomyoma. Cancer 120: 3165-77
337. Zhang Z, Zhang L, Yin ZY, et al. (2014b). miR-107 regulates cisplatin chemosensitivity of A549 non small cell lung cancer cell line by targeting cyclin dependent kinase 8. Int J Clin Exp Pathol 7: 7236-41
338. Zhao X, Feng D, Wang Q, et al. (2012). Regulation of lipogenesis by cyclin-dependent kinase 8-mediated control of SREBP-1. J Clin Invest 122: 2417-27
339. Zhou H, Kim S, Ishii S, Boyer TG. (2006). Mediator modulates Gli3-dependent Sonic hedgehog signaling. Mol Cell Biol 26: 8667-82
340. Zhou H, Spaeth JM, Kim NH, et al. (2012). MED12 mutations link intellectual disability syndromes with dysregulated GLI3-dependent Sonic Hedgehog signaling. Proc Natl Acad Sci USA 109: 19763-8