Regulation of stem cell function by protein ubiquitylation

EMBO Reports

Volumn 15, Issue 4, 2014, Pages 365-382

  Strikoudis, Alexandros ^a   Guillamot, Maria ^a   Aifantis, Iannis ^a  

^a NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

differentiation; malignancy; proteasome; stem cells; ubiquitin

Indexed keywords

ANTINEOPLASTIC AGENT; BETA CATENIN; BORTEZOMIB; IMIDAZOLINE DERIVATIVE; INDOLE DERIVATIVE; MYC PROTEIN; PROTEASOME; SMAD PROTEIN; SPIRO COMPOUND; TRANSCRIPTION FACTOR; UBIQUITIN; UBIQUITIN PROTEIN LIGASE E3; WNT PROTEIN; CHROMATIN; UBIQUITIN PROTEIN LIGASE;

ADENOMA; ADULT STEM CELL; CANCER STEM CELL; CARCINOGENESIS; CELL DIFFERENTIATION; CELL FUNCTION; CELL PROLIFERATION; CELL RENEWAL; CHROMATIN; CHROMATIN STRUCTURE; DNA METHYLATION; DNA REPLICATION; DRUG TARGETING; EMBRYONIC STEM CELL; HEMATOPOIETIC STEM CELL; HISTONE UBIQUITINATION; HOMEOSTASIS; HUMAN; INTESTINAL STEM CELL; MULTIPOTENT STEM CELL; NEURAL STEM CELL; NONHUMAN; NUCLEAR REPROGRAMMING; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN STABILITY; PROTEOMICS; REGULATORY MECHANISM; REVIEW; STEM CELL; UBIQUITINATION; ANIMAL; CELL DIVISION; GENETIC EPIGENESIS; METABOLISM; NEOPLASM; PATHOLOGY; PHYSIOLOGY;

ANIMALS; CELL DIFFERENTIATION; CELL DIVISION; CHROMATIN; EPIGENESIS, GENETIC; HUMANS; NEOPLASMS; NEURAL STEM CELLS; PROTEOLYSIS; STEM CELLS; UBIQUITIN-PROTEIN LIGASES; UBIQUITINATION;

EID: 84898637662     PISSN: 1469221X     EISSN: 14693178     Source Type: Journal    
DOI: 10.1002/embr.201338373     Document Type: Review

References (224)

1. Fuchs E, Chen T, (2013) A matter of life and death: self-renewal in stem cells. EMBO Rep 14: 39-48
2. He S, Nakada D, Morrison SJ, (2009) Mechanisms of stem cell self-renewal. Annu Rev Cell Dev Biol 25: 377-406
3. Passegue E, Wagers AJ, (2006) Regulating quiescence: new insights into hematopoietic stem cell biology. Dev Cell 10: 415-417
4. Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ, (2006) Purification and unique properties of mammary epithelial stem cells. Nature 439: 993-997 (Pubitemid 43292419)
5. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, et al (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449: 1003-1007 (Pubitemid 350014593)
6. Neumuller RA, Knoblich JA, (2009) Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancer. Genes Dev 23: 2675-2699
7. Gonczy P, (2008) Mechanisms of asymmetric cell division: flies and worms pave the way. Nat Rev Mol Cell Biol 9: 355-366 (Pubitemid 351574196)
8. Lobo NA, Shimono Y, Qian D, Clarke MF, (2007) The biology of cancer stem cells. Annu Rev Cell Dev Biol 23: 675-699
9. Catic A, Ploegh HL, (2005) Ubiquitin-conserved protein or selfish gene? Trends Biochem Sci 30: 600-604
10. Deshaies RJ, Joazeiro CA, (2009) RING domain E3 ubiquitin ligases. Annu Rev Biochem 78: 399-434
11. Kravtsova-Ivantsiv Y, Ciechanover A, (2012) Non-canonical ubiquitin-based signals for proteasomal degradation. J Cell Sci 125: 539-548
12. Jin L, Williamson A, Banerjee S, Philipp I, Rape M, (2008) Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell 133: 653-665 (Pubitemid 351636306)
13. Zeng W, Sun L, Jiang X, Chen X, Hou F, Adhikari A, Xu M, Chen ZJ, (2010) Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell 141: 315-330
14. Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, Chen ZJ, (2000) Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103: 351-361
15. Bedford L, Paine S, Sheppard PW, Mayer RJ, Roelofs J, (2010) Assembly, structure, and function of the 26S proteasome. Trends Cell Biol 20: 391-401
16. Sadowski M, Suryadinata R, Tan AR, Roesley SN, Sarcevic B, (2012) Protein monoubiquitination and polyubiquitination generate structural diversity to control distinct biological processes. IUBMB Life 64: 136-142
17. Komander D, Rape M, (2012) The ubiquitin code. Annu Rev Biochem 81: 203-229
18. Dikic I, Wakatsuki S, Walters KJ, (2009) Ubiquitin-binding domains-from structures to functions. Nat Rev Mol Cell Biol 10: 659-671
19. Marques AJ, Palanimurugan R, Matias AC, Ramos PC, Dohmen RJ, (2009) Catalytic mechanism and assembly of the proteasome. Chem Rev 109: 1509-1536
20. Husnjak K, Elsasser S, Zhang N, Chen X, Randles L, Shi Y, Hofmann K, Walters KJ, Finley D, Dikic I, (2008) Proteasome subunit Rpn13 is a novel ubiquitin receptor. Nature 453: 481-488 (Pubitemid 351733317)
21. Yao T, Cohen RE, (2002) A cryptic protease couples deubiquitination and degradation by the proteasome. Nature 419: 403-407
22. Smith DM, Chang SC, Park S, Finley D, Cheng Y, Goldberg AL, (2007) Docking of the proteasomal ATPases' carboxyl termini in the 20S proteasome's alpha ring opens the gate for substrate entry. Mol Cell 27: 731-744 (Pubitemid 47333222)
23. Sorokin AV, Kim ER, Ovchinnikov LP, (2009) Proteasome system of protein degradation and processing. Biochemistry (Mosc) 74: 1411-1442
24. Lander GC, Estrin E, Matyskiela ME, Bashore C, Nogales E, Martin A, (2012) Complete subunit architecture of the proteasome regulatory particle. Nature 482: 186-191
25. Caravita T, de Fabritiis P, Palumbo A, Amadori S, Boccadoro M, (2006) Bortezomib: efficacy comparisons in solid tumors and hematologic malignancies. Nat Clin Pract Oncol 3: 374-387 (Pubitemid 44027292)
26. Driscoll JJ, Woodle ES, (2012) Targeting the ubiquitin+proteasome system in solid tumors. Semin Hematol 49: 277-283
27. Anchoori RK, Karanam B, Peng S, Wang JW, Jiang R, Tanno T, Orlowski RZ, Matsui W, Zhao M, Rudek MA, et al (2013) A bis-benzylidine piperidone targeting proteasome ubiquitin receptor RPN13/ADRM1 as a therapy for cancer. Cancer Cell 24: 791-805
28. Metzger MB, Hristova VA, Weissman AM, (2012) HECT and RING finger families of E3 ubiquitin ligases at a glance. J Cell Sci 125: 531-537
29. Bernassola F, Karin M, Ciechanover A, Melino G, (2008) The HECT family of E3 ubiquitin ligases: multiple players in cancer development. Cancer Cell 14: 10-21 (Pubitemid 351885498)
30. Eisenhaber B, Chumak N, Eisenhaber F, Hauser MT, (2007) The ring between ring fingers (RBR) protein family. Genome Biol 8: 209
31. Smit JJ, Sixma TK, (2014) RBR E3-ligases at work. EMBO Rep 15: 142-154
32. Lau AW, Fukushima H, Wei W, (2012) The Fbw7 and betaTRCP E3 ubiquitin ligases and their roles in tumorigenesis. Front Biosci (Landmark Ed) 17: 2197-2212
33. Rossi M, Duan S, Jeong YT, Horn M, Saraf A, Florens L, Washburn MP, Antebi A, Pagano M, (2013) Regulation of the CRL4(Cdt2) ubiquitin ligase and cell-cycle exit by the SCF(Fbxo11) ubiquitin ligase. Mol Cell 49: 1159-1166
34. Fang J, Chen T, Chadwick B, Li E, Zhang Y, (2004) Ring1b-mediated H2A ubiquitination associates with inactive X chromosomes and is involved in initiation of X inactivation. J Biol Chem 279: 52812-52815 (Pubitemid 40051779)
35. Atanassov BS, Koutelou E, Dent SY, (2011) The role of deubiquitinating enzymes in chromatin regulation. FEBS Lett 585: 2016-2023
36. Evans MJ, Kaufman MH, (1981) Establishment in culture of pluripotential cells from mouse embryos. Nature 292: 154-156 (Pubitemid 11050741)
37. Martin GR, (1981) Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78: 7634-7638 (Pubitemid 12186197)
38. Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, et al (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122: 947-956 (Pubitemid 41345211)
39. Niwa H, Miyazaki J, Smith AG, (2000) Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 24: 372-376 (Pubitemid 30187435)
40. Xu H, Wang W, Li C, Yu H, Yang A, Wang B, Jin Y, (2009) WWP2 promotes degradation of transcription factor OCT4 in human embryonic stem cells. Cell Res 19: 561-573
41. Xu HM, et al (2004) Wwp2, an E3 ubiquitin ligase that targets transcription factor Oct-4 for ubiquitination. J Biol Chem 279: 23495-23503 (Pubitemid 38685661)
42. Liao B, Jin Y, (2010) Wwp2 mediates Oct4 ubiquitination and its own auto-ubiquitination in a dosage-dependent manner. Cell Res 20: 332-344
43. Takahashi K, Yamanaka S, (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663-676 (Pubitemid 44233629)
44. Buckley SM, Aranda-Orgilles B, Strikoudis A, Apostolou E, Loizou E, Moran-Crusio K, Farnsworth CL, Koller AA, Dasgupta R, Silva JC, et al (2012) Regulation of pluripotency and cellular reprogramming by the ubiquitin-proteasome system. Cell Stem Cell 11: 783-798
45. Gregory MA, Qi Y, Hann SR, (2003) Phosphorylation by glycogen synthase kinase-3 controls c-myc proteolysis and subnuclear localization. J Biol Chem 278: 51606-51612 (Pubitemid 38020405)
46. Ramakrishna S, Suresh B, Lim KH, Cha BH, Lee SH, Kim KS, Baek KH, (2011) PEST motif sequence regulating human NANOG for proteasomal degradation. Stem Cells Dev 20: 1511-1519
47. Moretto-Zita M, Jin H, Shen Z, Zhao T, Briggs SP, Xu Y, (2010) Phosphorylation stabilizes Nanog by promoting its interaction with Pin1. Proc Natl Acad Sci U S A 107: 13312-13317
48. Yates A, Chambers I, (2005) The homeodomain protein Nanog and pluripotency in mouse embryonic stem cells. Biochem Soc Trans 33: 1518-1521 (Pubitemid 41779728)
49. Chambers I, Colby D, Robertson M, Nichols J, Lee S, Tweedie S, Smith A, (2003) Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells. Cell 113: 643-655 (Pubitemid 36694189)
50. Ye F, Zhou C, Cheng Q, Shen J, Chen H, (2008) Stem-cell-abundant proteins Nanog, Nucleostemin and Musashi1 are highly expressed in malignant cervical epithelial cells. BMC Cancer 8: 108
51. Meng HM, Zheng P, Wang XY, Liu C, Sui HM, Wu SJ, Zhou J, Ding YQ, Li JM, (2010) Overexpression of Nanog predicts tumor progression and poor prognosis in colorectal cancer. Cancer Biol Ther 9: 295-302
52. Yang Y, Niu CS, Cheng CD, (2013) Pin1-Nanog expression in human glioma is correlated with advanced tumor progression. Oncol Rep 30: 560-566
53. Jin L, Pahuja KB, Wickliffe KE, Gorur A, Baumgartel C, Schekman R, Rape M, (2012) Ubiquitin-dependent regulation of COPII coat size and function. Nature 482: 495-500
54. Gao S, Alarcon C, Sapkota G, Rahman S, Chen PY, Goerner N, Macias MJ, Erdjument , Bromage H, Tempst P, et al (2009) Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling. Mol Cell 36: 457-468
55. Zhang L, Huang H, Zhou F, Schimmel J, Pardo CG, Zhang T, Barakat TS, Sheppard KA, Mickanin C, Porter JA, et al (2012) RNF12 controls embryonic stem cell fate and morphogenesis in zebrafish embryos by targeting Smad7 for degradation. Mol Cell 46: 650-661
56. Hernebring M, Fredriksson A, Liljevald M, Cvijovic M, Norrman K, Wiseman J, Semb H, Nystrom T, (2013) Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28. Sci Rep 3: 1381
57. Hernebring M, Brolen G, Aguilaniu H, Semb H, Nystrom T, (2006) Elimination of damaged proteins during differentiation of embryonic stem cells. Proc Natl Acad Sci U S A 103: 7700-7705
58. Vilchez D, Boyer L, Morantte I, Lutz M, Merkwirth C, Joyce D, Spencer B, Page L, Masliah E, Berggren WT, et al (2012) Increased proteasome activity in human embryonic stem cells is regulated by PSMD11. Nature 489: 304-308
59. Szutorisz H, Georgiou A, Tora L, Dillon N, (2006) The proteasome restricts permissive transcription at tissue-specific gene loci in embryonic stem cells. Cell 127: 1375-1388 (Pubitemid 44960411)
60. Babaie Y, Herwig R, Greber B, Brink TC, Wruck W, Groth D, Lehrach H, Burdon T, Adjaye J, (2007) Analysis of Oct4-dependent transcriptional networks regulating self-renewal and pluripotency in human embryonic stem cells. Stem Cells 25: 500-510 (Pubitemid 46232806)
61. Orkin SH, Zon LI, (2008) Hematopoiesis: an evolving paradigm for stem cell biology. Cell 132: 631-644 (Pubitemid 351260057)
62. Mikkola HK, Orkin SH, (2006) The journey of developing hematopoietic stem cells. Development 133: 3733-3744 (Pubitemid 44650952)
63. Wilson A, Trumpp A, (2006) Bone-marrow haematopoietic-stem-cell niches. Nat Rev Immunol 6: 93-106 (Pubitemid 43361585)
64. Jude CD, Gaudet JJ, Speck NA, Ernst P, (2008) Leukemia and hematopoietic stem cells: balancing proliferation and quiescence. Cell Cycle 7: 586-591 (Pubitemid 351506325)
65. Warr MR, Pietras EM, Passegue E, (2011) Mechanisms controlling hematopoietic stem cell functions during normal hematopoiesis and hematological malignancies. Wiley Interdiscip Rev Syst Biol Med 3: 681-701
66. Trumpp A, Essers M, Wilson A, (2010) Awakening dormant haematopoietic stem cells. Nat Rev Immunol 10: 201-209
67. Lacombe J, Herblot S, Rojas-Sutterlin S, Haman A, Barakat S, Iscove NN, Sauvageau G, Hoang T, (2010) Scl regulates the quiescence and the long-term competence of hematopoietic stem cells. Blood 115: 792-803
68. Laurenti E, Varnum-Finney B, Wilson A, Ferrero I, Blanco-Bose WE, Ehninger A, Knoepfler PS, Cheng PF, MacDonald HR, Eisenman RN, et al (2008) Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity. Cell Stem Cell 3: 611-624
69. Lessard J, Sauvageau G, (2003) Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 423: 255-260 (Pubitemid 40852690)
70. Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, Morrison SJ, Clarke MF, (2003) Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423: 302-305 (Pubitemid 40852701)
71. Reavie L, Della Gatta G, Crusio K, Aranda-Orgilles B, Buckley SM, Thompson B, Lee E, Gao J, Bredemeyer AL, Helmink BA, et al (2010) Regulation of hematopoietic stem cell differentiation by a single ubiquitin ligase-substrate complex. Nat Immunol 11: 207-215
72. Wilson A, Murphy MJ, Oskarsson T, Kaloulis K, Bettess MD, Oser GM, Pasche AC, Knabenhans C, Macdonald HR, Trumpp A, (2004) c-Myc controls the balance between hematopoietic stem cell self-renewal and differentiation. Genes Dev 18: 2747-2763 (Pubitemid 39507768)
73. Pietras EM, Warr MR, Passegue E, (2011) Cell cycle regulation in hematopoietic stem cells. J Cell Biol 195: 709-720
74. Matsuoka S, Oike Y, Onoyama I, Iwama A, Arai F, Takubo K, Mashimo Y, Oguro H, Nitta E, Ito K, et al (2008) Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL. Genes Dev 22: 986-991 (Pubitemid 351544237)
75. King B, Trimarchi T, Reavie L, Xu L, Mullenders J, Ntziachristos P, Aranda-Orgilles B, Perez-Garcia A, Shi J, Vakoc C, et al (2013) The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability. Cell 153: 1552-1566
76. Moran-Crusio K, Reavie LB, Aifantis I, (2012) Regulation of hematopoietic stem cell fate by the ubiquitin proteasome system. Trends Immunol 33: 357-363
77. Matsumoto A, Nakayama KI, (2013) Role of key regulators of the cell cycle in maintenance of hematopoietic stem cells. Biochim Biophys Acta 1830: 2335-2344
78. Li J, (2011) Quiescence regulators for hematopoietic stem cell. Exp Hematol 39: 511-520
79. Jehn BM, Dittert I, Beyer S, von der Mark K, Bielke W, (2002) c-Cbl binding and ubiquitin-dependent lysosomal degradation of membrane-associated Notch1. J Biol Chem 277: 8033-8040 (Pubitemid 34968255)
80. Zeng S, Xu Z, Lipkowitz S, Longley JB, (2005) Regulation of stem cell factor receptor signaling by Cbl family proteins (Cbl-b/c-Cbl). Blood 105: 226-232 (Pubitemid 40053087)
81. Goh EL, Zhu T, Leong WY, Lobie PE, (2002) c-Cbl is a negative regulator of GH-stimulated STAT5-mediated transcription. Endocrinology 143: 3590-3603 (Pubitemid 34925736)
82. Schmidt MH, Dikic I, (2005) The Cbl interactome and its functions. Nat Rev Mol Cell Biol 6: 907-918 (Pubitemid 41778710)
83. Rathinam C, Thien CB, Langdon WY, Gu H, Flavell RA, (2008) The E3 ubiquitin ligase c-Cbl restricts development and functions of hematopoietic stem cells. Genes Dev 22: 992-997 (Pubitemid 351544238)
84. Rathinam C, Thien CB, Flavell RA, Langdon WY, (2010) Myeloid leukemia development in c-Cbl RING finger mutant mice is dependent on FLT3 signaling. Cancer Cell 18: 341-352
85. Bacher U, Haferlach C, Schnittger S, Kohlmann A, Kern W, Haferlach T, (2010) Mutations of the TET2 and CBL genes: novel molecular markers in myeloid malignancies. Ann Hematol 89: 643-652
86. Barresi V, Palumbo GA, Musso N, Consoli C, Capizzi C, Meli CR, Romano A, Di Raimondo F, Condorelli DF, (2010) Clonal selection of 11q CN-LOH and CBL gene mutation in a serially studied patient during MDS progression to AML. Leuk Res 34: 1539-1542
87. Fernandes MS, Reddy MM, Croteau NJ, Walz C, Weisbach H, Podar K, Band H, Carroll M, Reiter A, Larson RA, et al (2010) Novel oncogenic mutations of CBL in human acute myeloid leukemia that activate growth and survival pathways depend on increased metabolism. J Biol Chem 285: 32596-32605
88. Rocquain J, Carbuccia N, Trouplin V, Raynaud S, Murati A, Nezri M, Tadrist Z, Olschwang S, Vey N, Birnbaum D, et al (2010) Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias. BMC Cancer 10: 401
89. Tefferi A, (2010) Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia 24: 1128-1138
90. Rathinam C, Matesic LE, Flavell RA, (2011) The E3 ligase Itch is a negative regulator of the homeostasis and function of hematopoietic stem cells. Nat Immunol 12: 399-407
91. Akhoondi S, Sun D, von der Lehr N, Apostolidou S, Klotz K, Maljukova A, Cepeda D, Fiegl H, Dafou D, Marth C, et al (2007) FBXW7/hCDC4 is a general tumor suppressor in human cancer. Cancer Res 67: 9006-9012 (Pubitemid 47535882)
92. O'Neil J, Grim J, Strack P, Rao S, Tibbitts D, Winter C, Hardwick J, Welcker M, Meijerink JP, Pieters R, et al (2007) FBW7 mutations in leukemic cells mediate NOTCH pathway activation and resistance to gamma-secretase inhibitors. J Exp Med 204: 1813-1824 (Pubitemid 47236319)
93. Thompson BJ, Buonamici S, Sulis ML, Palomero T, Vilimas T, Basso G, Ferrando A, Aifantis I, (2007) The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia. J Exp Med 204: 1825-1835 (Pubitemid 47236320)
94. Gupta-Rossi N, Le Bail O, Gonen H, Brou C, Logeat F, Six E, Ciechanover A, Israel A, (2001) Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor. J Biol Chem 276: 34371-34378
95. Tsunematsu R, Nakayama K, Oike Y, Nishiyama M, Ishida N, Hatakeyama S, Bessho Y, Kageyama R, Suda T, Nakayama KI, (2004) Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development. J Biol Chem 279: 9417-9423 (Pubitemid 38296008)
96. Welcker M, Orian A, Jin J, Grim JE, Harper JW, Eisenman RN, Clurman BE, (2004) The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proc Natl Acad Sci U S A 101: 9085-9090 (Pubitemid 38781615)
97. Yada M, Hatakeyama S, Kamura T, Nishiyama M, Tsunematsu R, Imaki H, Ishida N, Okumura F, Nakayama K, Nakayama KI, (2004) Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J 23: 2116-2125 (Pubitemid 38737738)
98. Koepp DM, Schaefer LK, Ye X, Keyomarsi K, Chu C, Harper JW, Elledge SJ, (2001) Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science 294: 173-177 (Pubitemid 32952972)
99. Strohmaier H, Spruck CH, Kaiser P, Won KA, Sangfelt O, Reed SI, (2001) Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature 413: 316-322 (Pubitemid 32905853)
100. Inuzuka H, Shaik S, Onoyama I, Gao D, Tseng A, Maser RS, Zhai B, Wan L, Gutierrez A, Lau AW, et al (2011) SCF(FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction. Nature 471: 104-109
101. Wertz IE, Kusam S, Lam C, Okamoto T, Sandoval W, Anderson DJ, Helgason E, Ernst JA, Eby M, Liu J, et al (2011) Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7. Nature 471: 110-114
102. Thompson BJ, Jankovic V, Gao J, Buonamici S, Vest A, Lee JM, Zavadil J, Nimer SD, Aifantis I, (2008) Control of hematopoietic stem cell quiescence by the E3 ubiquitin ligase Fbw7. J Exp Med 205: 1395-1408 (Pubitemid 351831495)
103. Onoyama I, Tsunematsu R, Matsumoto A, Kimura T, de Alboran IM, Nakayama K, Nakayama KI, (2007) Conditional inactivation of Fbxw7 impairs cell-cycle exit during T cell differentiation and results in lymphomatogenesis. J Exp Med 204: 2875-2888 (Pubitemid 350179557)
104. Nakayama K, Nagahama H, Minamishima YA, Miyake S, Ishida N, Hatakeyama S, Kitagawa M, Iemura S, Natsume T, Nakayama KI, (2004) Skp2-mediated degradation of p27 regulates progression into mitosis. Dev Cell 6: 661-672 (Pubitemid 38579350)
105. Frescas D, Pagano M, (2008) Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer. Nat Rev Cancer 8: 438-449 (Pubitemid 351744963)
106. Rodriguez S, Wang L, Mumaw C, Srour EF, Lo Celso C, Nakayama K, Carlesso N, (2011) The SKP2 E3 ligase regulates basal homeostasis and stress-induced regeneration of HSCs. Blood 117: 6509-6519
107. Wang J, Han F, Wu J, Lee SW, Chan CH, Wu CY, Yang WL, Gao Y, Zhang X, Jeong YS, et al (2011) The role of Skp2 in hematopoietic stem cell quiescence, pool size, and self-renewal. Blood 118: 5429-5438
108. Parmar K, Mauch P, Vergilio JA, Sackstein R, Down JD, (2007) Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. Proc Natl Acad Sci U S A 104: 5431-5436 (Pubitemid 47175697)
109. Takubo K, Goda N, Yamada W, Iriuchishima H, Ikeda E, Kubota Y, Shima H, Johnson RS, Hirao A, Suematsu M, et al (2010) Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. Cell Stem Cell 7: 391-402
110. Abbas HA, Maccio DR, Coskun S, Jackson JG, Hazen AL, Sills TM, You MJ, Hirschi KK, Lozano G, (2010) Mdm2 is required for survival of hematopoietic stem cells/progenitors via dampening of ROS-induced p53 activity. Cell Stem Cell 7: 606-617
111. Jones SN, Roe AE, Donehower LA, Bradley A, (1995) Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature 378: 206-208
112. Montes de Oca Luna R, Wagner DS, Lozano G, (1995) Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature 378: 203-206
113. D'Andrea AD, Grompe M, (2003) The Fanconi anaemia/BRCA pathway. Nat Rev Cancer 3: 23-34 (Pubitemid 37328884)
114. Nijman SM, Huang TT, Dirac AM, Brummelkamp TR, Kerkhoven RM, D'Andrea AD, Bernards R, (2005) The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. Mol Cell 17: 331-339 (Pubitemid 40193305)
115. Kim JM, Parmar K, Huang M, Weinstock DM, Ruit CA, Kutok JL, D'Andrea AD, (2009) Inactivation of murine Usp1 results in genomic instability and a Fanconi anemia phenotype. Dev Cell 16: 314-320
116. Parmar K, Kim J, Sykes SM, Shimamura A, Stuckert P, Zhu K, Hamilton A, Deloach MK, Kutok JL, Akashi K, et al (2010) Hematopoietic stem cell defects in mice with deficiency of Fancd2 or Usp1. Stem Cells 28: 1186-1195
117. Joenje H, Patel KJ, (2001) The emerging genetic and molecular basis of Fanconi anaemia. Nat Rev Genet 2: 446-457 (Pubitemid 33673411)
118. Malanchi I, Peinado H, Kassen D, Hussenet T, Metzger D, Chambon P, Huber M, Hohl D, Cano A, Birchmeier W, et al (2008) Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling. Nature 452: 650-653 (Pubitemid 351483363)
119. Ito M, Yang Z, Andl T, Cui C, Kim N, Millar SE, Cotsarelis G, (2007) Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 447: 316-320 (Pubitemid 46788832)
120. Solanas G, Benitah SA, (2013) Regenerating the skin: a task for the heterogeneous stem cell pool and surrounding niche. Nat Rev Mol Cell Biol 14: 737-748
121. Perez-Losada J, Balmain A, (2003) Stem-cell hierarchy in skin cancer. Nat Rev Cancer 3: 434-443 (Pubitemid 37328847)
122. Reya T, Clevers H, (2005) Wnt signalling in stem cells and cancer. Nature 434: 843-850 (Pubitemid 40558990)
123. Silva-Vargas V, Lo Celso C, Giangreco A, Ofstad T, Prowse DM, Braun KM, Watt FM, (2005) Beta-catenin and Hedgehog signal strength can specify number and location of hair follicles in adult epidermis without recruitment of bulge stem cells. Dev Cell 9: 121-131 (Pubitemid 40903665)
124. Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W, (2001) beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105: 533-545 (Pubitemid 32520858)
125. Han G, Li AG, Liang YY, Owens P, He W, Lu S, Yoshimatsu Y, Wang D, Ten Dijke P, Lin X, et al (2006) Smad7-induced beta-catenin degradation alters epidermal appendage development. Dev Cell 11: 301-312 (Pubitemid 44283940)
126. Perry WL, Hustad CM, Swing DA, O'Sullivan TN, Jenkins NA, Copeland NG, (1998) The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a18H mice. Nat Genet 18: 143-146 (Pubitemid 28082460)
127. Rossi M, Aqeilan RI, Neale M, Candi E, Salomoni P, Knight RA, Croce CM, Melino G, (2006) The E3 ubiquitin ligase Itch controls the protein stability of p63. Proc Natl Acad Sci U S A 103: 12753-12758 (Pubitemid 44298633)
128. Rossi M, De Simone M, Pollice A, Santoro R, La Mantia G, Guerrini L, Calabro V, (2006) Itch/AIP4 associates with and promotes p63 protein degradation. Cell Cycle 5: 1816-1822 (Pubitemid 44435325)
129. Qiu L, Joazeiro C, Fang N, Wang HY, Elly C, Altman Y, Fang D, Hunter T, Liu YC, (2000) Recognition and ubiquitination of Notch by Itch, a hect-type E3 ubiquitin ligase. J Biol Chem 275: 35734-35737
130. Candi E, Schmidt R, Melino G, (2005) The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 6: 328-340 (Pubitemid 40516899)
131. Fang D, Elly C, Gao B, Fang N, Altman Y, Joazeiro C, Hunter T, Copeland N, Jenkins N, Liu YC, (2002) Dysregulation of T lymphocyte function in itchy mice: a role for Itch in TH2 differentiation. Nat Immunol 3: 281-287 (Pubitemid 34213430)
132. Melino G, Gallagher E, Aqeilan RI, Knight R, Peschiaroli A, Rossi M, Scialpi F, Malatesta M, Zocchi L, Browne G, et al (2008) Itch: a HECT-type E3 ligase regulating immunity, skin and cancer. Cell Death Differ 15: 1103-1112 (Pubitemid 351850962)
133. Candi E, Rufini A, Terrinoni A, Dinsdale D, Ranalli M, Paradisi A, De Laurenzi V, Spagnoli LG, Catani MV, Ramadan S, et al (2006) Differential roles of p63 isoforms in epidermal development: selective genetic complementation in p63 null mice. Cell Death Differ 13: 1037-1047
134. Galli F, Rossi M, D'Alessandra Y, De Simone M, Lopardo T, Haupt Y, Alsheich-Bartok O, Anzi S, Shaulian E, Calabro V, et al (2010) MDM2 and Fbw7 cooperate to induce p63 protein degradation following DNA damage and cell differentiation. J Cell Sci 123: 2423-2433
135. van der Flier LG, Clevers H, (2009) Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 71: 241-260
136. Logan CY, Nusse R, (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20: 781-810 (Pubitemid 39488658)
137. Hart M, Concordet JP, Lassot I, Albert I, del los Santos R, Durand H, Perret C, Rubinfeld B, Margottin F, Benarous R, et al (1999) The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell. Curr Biol 9: 207-210 (Pubitemid 29120385)
138. Ilyas M, Tomlinson IP, Rowan A, Pignatelli M, Bodmer WF, (1997) Beta-catenin mutations in cell lines established from human colorectal cancers. Proc Natl Acad Sci U S A 94: 10330-10334 (Pubitemid 27407041)
139. Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW, (1997) Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 275: 1787-1790 (Pubitemid 27136715)
140. Kudo Y, Guardavaccaro D, Santamaria PG, Koyama-Nasu R, Latres E, Bronson R, Yamasaki L, Pagano M, (2004) Role of F-box protein betaTrcp1 in mammary gland development and tumorigenesis. Mol Cell Biol 24: 8184-8194 (Pubitemid 39167466)
141. Belaidouni N, Peuchmaur M, Perret C, Florentin A, Benarous R, Besnard-Guerin C, (2005) Overexpression of human beta TrCP1 deleted of its F box induces tumorigenesis in transgenic mice. Oncogene 24: 2271-2276 (Pubitemid 40516593)
142. Koo BK, Spit M, Jordens I, Low TY, Stange DE, van de Wetering M, van Es JH, Mohammed S, Heck AJ, Maurice MM, et al (2012) Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature 488: 665-669
143. Babaei-Jadidi R, Li N, Saadeddin A, Spencer-Dene B, Jandke A, Muhammad B, Ibrahim EE, Muraleedharan R, Abuzinadah M, Davis H, et al (2011) FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation. J Exp Med 208: 295-312
144. Yoon K, Gaiano N, (2005) Notch signaling in the mammalian central nervous system: insights from mouse mutants. Nat Neurosci 8: 709-715 (Pubitemid 43085834)
145. Gaiano N, Nye JS, Fishell G, (2000) Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron 26: 395-404
146. Koo BK, Lim HS, Song R, Yoon MJ, Yoon KJ, Moon JS, Kim YW, Kwon MC, Yoo KW, Kong MP, et al (2005) Mind bomb 1 is essential for generating functional Notch ligands to activate Notch. Development 132: 3459-3470 (Pubitemid 41246120)
147. Itoh M, Kim CH, Palardy G, Oda T, Jiang YJ, Maust D, Yeo SY, Lorick K, Wright GJ, Ariza-McNaughton L, et al (2003) Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta. Dev Cell 4: 67-82 (Pubitemid 36109145)
148. Westbrook TF, Hu G, Ang XL, Mulligan P, Pavlova NN, Liang A, Leng Y, Maehr R, Shi Y, Harper JW, et al (2008) SCFbeta-TRCP controls oncogenic transformation and neural differentiation through REST degradation. Nature 452: 370-374 (Pubitemid 351430796)
149. Zhao X, Heng JI, Guardavaccaro D, Jiang R, Pagano M, Guillemot F, Iavarone A, Lasorella A, (2008) The HECT-domain ubiquitin ligase Huwe1 controls neural differentiation and proliferation by destabilizing the N-Myc oncoprotein. Nat Cell Biol 10: 643-653 (Pubitemid 351772930)
150. Chu J, Hong NA, Masuda CA, Jenkins BV, Nelms KA, Goodnow CC, Glynne RJ, Wu H, Masliah E, Joazeiro CA, et al (2009) A mouse forward genetics screen identifies LISTERIN as an E3 ubiquitin ligase involved in neurodegeneration. Proc Natl Acad Sci U S A 106: 2097-2103
151. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N, (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392: 605-608 (Pubitemid 28207717)
152. Zhang Y, Gao J, Chung KK, Huang H, Dawson VL, Dawson TM, (2000) Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc Natl Acad Sci U S A 97: 13354-13359
153. Dawson TM, Dawson VL, (2003) Molecular pathways of neurodegeneration in Parkinson's disease. Science 302: 819-822 (Pubitemid 37339614)
154. Strahl BD, Allis CD, (2000) The language of covalent histone modifications. Nature 403: 41-45 (Pubitemid 30038513)
155. Cao J, Yan Q, (2012) Histone ubiquitination and deubiquitination in transcription, DNA damage response, and cancer. Front Oncol 2: 26
156. Kim J, Hake SB, Roeder RG, (2005) The human homolog of yeast BRE1 functions as a transcriptional coactivator through direct activator interactions. Mol Cell 20: 759-770 (Pubitemid 41740697)
157. Kim J, Guermah M, McGinty RK, Lee JS, Tang Z, Milne TA, Shilatifard A, Muir TW, Roeder RG, (2009) RAD6-Mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells. Cell 137: 459-471
158. Zhou W, Zhu P, Wang J, Pascual G, Ohgi KA, Lozach J, Glass CK, Rosenfeld MG, (2008) Histone H2A monoubiquitination represses transcription by inhibiting RNA polymerase II transcriptional elongation. Mol Cell 29: 69-80
159. Pavri R, Zhu B, Li G, Trojer P, Mandal S, Shilatifard A, Reinberg D, (2006) Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II. Cell 125: 703-717 (Pubitemid 43732350)
160. Minsky N, Shema E, Field Y, Schuster M, Segal E, Oren M, (2008) Monoubiquitinated H2B is associated with the transcribed region of highly expressed genes in human cells. Nat Cell Biol 10: 483-488
161. Shema E, Tirosh I, Aylon Y, Huang J, Ye C, Moskovits N, Raver-Shapira N, Minsky N, Pirngruber J, Tarcic G, et al (2008) The histone H2B-specific ubiquitin ligase RNF20/hBRE1 acts as a putative tumor suppressor through selective regulation of gene expression. Genes Dev 22: 2664-2676
162. Xiao T, Kao CF, Krogan NJ, Sun ZW, Greenblatt JF, Osley MA, Strahl BD, (2005) Histone H2B ubiquitylation is associated with elongating RNA polymerase II. Mol Cell Biol 25: 637-651 (Pubitemid 40096585)
163. Fierz B, Chatterjee C, McGinty RK, Bar-Dagan M, Raleigh DP, Muir TW, (2011) Histone H2B ubiquitylation disrupts local and higher-order chromatin compaction. Nat Chem Biol 7: 113-119
164. Laribee RN, Fuchs SM, Strahl BD, (2007) H2B ubiquitylation in transcriptional control: a FACT-finding mission. Genes Dev 21: 737-743 (Pubitemid 46572353)
165. Jaehning JA, (2010) The Paf1 complex: platform or player in RNA polymerase II transcription? Biochim Biophys Acta 1799: 379-388
166. Karpiuk O, Najafova Z, Kramer F, Hennion M, Galonska C, Konig A, Snaidero N, Vogel T, Shchebet A, Begus-Nahrmann Y, et al (2012) The histone H2B monoubiquitination regulatory pathway is required for differentiation of multipotent stem cells. Mol Cell 46: 705-713
167. Fuchs G, Shema E, Vesterman R, Kotler E, Wolchinsky Z, Wilder S, Golomb L, Pribluda A, Zhang F, Haj-Yahya M, et al (2012) RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation. Mol Cell 46: 662-673
168. Vethantham V, Yang Y, Bowman C, Asp P, Lee JH, Skalnik DG, Dynlacht BD, (2012) Dynamic loss of H2B ubiquitylation without corresponding changes in H3K4 trimethylation during myogenic differentiation. Mol Cell Biol 32: 1044-1055
169. Chandrasekharan MB, Huang F, Sun ZW, (2010) Histone H2B ubiquitination and beyond: regulation of nucleosome stability, chromatin dynamics and the trans-histone H3 methylation. Epigenetics 5: 460-468
170. Zhao Y, Lang G, Ito S, Bonnet J, Metzger E, Sawatsubashi S, Suzuki E, Le Guezennec X, Stunnenberg HG, Krasnov A, et al (2008) A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing. Mol Cell 29: 92-101
171. Zhang XY, Varthi M, Sykes SM, Phillips C, Warzecha C, Zhu W, Wyce A, Thorne AW, Berger SL, McMahon SB, (2008) The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression. Mol Cell 29: 102-111
172. Piao S, Liu Y, Hu J, Guo F, Ma J, Sun Y, Zhang B, (2012) USP22 is useful as a novel molecular marker for predicting disease progression and patient prognosis of oral squamous cell carcinoma. PLoS One 7: e42540
173. Zhang Y, Yao L, Zhang X, Ji H, Wang L, Sun S, Pang D, (2011) Elevated expression of USP22 in correlation with poor prognosis in patients with invasive breast cancer. J Cancer Res Clin Oncol 137: 1245-1253
174. Buszczak M, Paterno S, Spradling AC, (2009) Drosophila stem cells share a common requirement for the histone H2B ubiquitin protease scrawny. Science 323: 248-251
175. Wang H, Wang L, Erdjument-Bromage H, Vidal M, Tempst P, Jones RS, Zhang Y, (2004) Role of histone H2A ubiquitination in Polycomb silencing. Nature 431: 873-878 (Pubitemid 39434086)
176. Cao R, Tsukada Y, Zhang Y, (2005) Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell 20: 845-854 (Pubitemid 41814874)
177. de Napoles M, Mermoud JE, Wakao R, Tang YA, Endoh M, Appanah R, Nesterova TB, Silva J, Otte AP, Vidal M, et al (2004) Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation. Dev Cell 7: 663-676 (Pubitemid 39462687)
178. Stock JK, Giadrossi S, Casanova M, Brookes E, Vidal M, Koseki H, Brockdorff N, Fisher AG, Pombo A, (2007) Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells. Nat Cell Biol 9: 1428-1435 (Pubitemid 350201756)
179. Wei J, Zhai L, Xu J, Wang H, (2006) Role of Bmi1 in H2A ubiquitylation and Hox gene silencing. J Biol Chem 281: 22537-22544
180. Buchwald G, van der Stoop P, Weichenrieder O, Perrakis A, van Lohuizen M, Sixma TK, (2006) Structure and E3-ligase activity of the Ring-Ring complex of polycomb proteins Bmi1 and Ring1b. EMBO J 25: 2465-2474 (Pubitemid 44012229)
181. Sauvageau M, Sauvageau G, (2010) Polycomb group proteins: multi-faceted regulators of somatic stem cells and cancer. Cell Stem Cell 7: 299-313
182. Molofsky AV, He S, Bydon M, Morrison SJ, Pardal R, (2005) Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes Dev 19: 1432-1437 (Pubitemid 41003009)
183. Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ, (2003) Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425: 962-967 (Pubitemid 37376927)
184. Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, Diehn M, Liu H, Panula SP, Chiao E, et al (2009) Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell 138: 592-603
185. Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ, (2002) Autoubiquitination of the BRCA1 BARD1 RING ubiquitin ligase. J Biol Chem 277: 22085-22092 (Pubitemid 34952363)
186. Xia Y, Pao GM, Chen HW, Verma IM, Hunter T, (2003) Enhancement of BRCA1 E3 ubiquitin ligase activity through direct interaction with the BARD1 protein. J Biol Chem 278: 5255-5263 (Pubitemid 36801039)
187. Zhu Q, Pao GM, Huynh AM, Suh H, Tonnu N, Nederlof PM, Gage FH, Verma IM, (2011) BRCA1 tumour suppression occurs via heterochromatin-mediated silencing. Nature 477: 179-184
188. Visvader JE, (2009) Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis. Genes Dev 23: 2563-2577
189. Lim E, Vaillant F, Wu D, Forrest NC, Pal B, Hart AH, Asselin-Labat ML, Gyorki DE, Ward T, Partanen A, et al (2009) Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med 15: 907-913
190. Joo HY, Zhai L, Yang C, Nie S, Erdjument-Bromage H, Tempst P, Chang C, Wang H, (2007) Regulation of cell cycle progression and gene expression by H2A deubiquitination. Nature 449: 1068-1072 (Pubitemid 350014605)
191. Shanbhag NM, Rafalska-Metcalf IU, Balane-Bolivar C, Janicki SM, Greenberg RA, (2010) ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks. Cell 141: 970-981
192. Scheuermann JC, de Ayala Alonso AG, Oktaba K, Ly-Hartig N, McGinty RK, Fraterman S, Wilm M, Muir TW, Muller J, (2010) Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature 465: 243-247
193. Dey A, Seshasayee D, Noubade R, French DM, Liu J, Chaurushiya MS, Kirkpatrick DS, Pham VC, Lill JR, Bakalarski CE, et al (2012) Loss of the tumor suppressor BAP1 causes myeloid transformation. Science 337: 1541-1546
194. Abdel-Wahab O, Gao J, Adli M, Dey A, Trimarchi T, Chung YR, Kuscu C, Hricik T, Ndiaye-Lobry D, Lafave LM, et al (2013) Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo. J Exp Med 210: 2641-2659
195. Mailand N, Bekker-Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, Lukas J, (2007) RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131: 887-900 (Pubitemid 350138084)
196. Stewart GS, Panier S, Townsend K, Al-Hakim AK, Kolas NK, Miller ES, Nakada S, Ylanko J, Olivarius S, Mendez M, et al (2009) The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. Cell 136: 420-434
197. Wang H, Zhai L, Xu J, Joo HY, Jackson S, Erdjument-Bromage H, Tempst P, Xiong Y, Zhang Y, (2006) Histone H3 and H4 ubiquitylation by the CUL4-DDB-ROC1 ubiquitin ligase facilitates cellular response to DNA damage. Mol Cell 22: 383-394 (Pubitemid 44308132)
198. Pham AD, Sauer F, (2000) Ubiquitin-activating/conjugating activity of TAFII250, a mediator of activation of gene expression in Drosophila. Science 289: 2357-2360
199. Nishiyama A, Yamaguchi L, Sharif J, Johmura Y, Kawamura T, Nakanishi K, Shimamura S, Arita K, Kodama T, Ishikawa F, et al (2013) Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication. Nature 502: 249-253
200. Bostick M, Kim JK, Esteve PO, Clark A, Pradhan S, Jacobsen SE, (2007) UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science 317: 1760-1764 (Pubitemid 47461842)
201. Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo TA, Shinga J, Mizutani-Koseki Y, Toyoda T, Okamura K, et al (2007) The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature 450: 908-912 (Pubitemid 350231331)
202. Williams K, Christensen J, Helin K, (2012) DNA methylation: TET proteins-guardians of CpG islands? EMBO Rep 13: 28-35
203. Meacham CE, Morrison SJ, (2013) Tumour heterogeneity and cancer cell plasticity. Nature 501: 328-337
204. Hoeller D, Hecker CM, Dikic I, (2006) Ubiquitin and ubiquitin-like proteins in cancer pathogenesis. Nat Rev Cancer 6: 776-788 (Pubitemid 44450466)
205. Nakayama KI, Nakayama K, (2006) Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer 6: 369-381
206. Malyukova A, Dohda T, von der Lehr N, Akhoondi S, Corcoran M, Heyman M, Spruck C, Grander D, Lendahl U, Sangfelt O, (2007) The tumor suppressor gene hCDC4 is frequently mutated in human T-cell acute lymphoblastic leukemia with functional consequences for Notch signaling. Cancer Res 67: 5611-5616 (Pubitemid 46984990)
207. Lee JW, Soung YH, Kim HJ, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH, (2006) Mutational analysis of the hCDC4 gene in gastric carcinomas. Eur J Cancer 42: 2369-2373 (Pubitemid 44307614)
208. Low J, Blosser W, Dowless M, Ricci-Vitiani L, Pallini R, de Maria R, Stancato L, (2012) Knockdown of ubiquitin ligases in glioblastoma cancer stem cells leads to cell death and differentiation. J Biomol Screen 17: 152-162
209. Micel LN, Tentler JJ, Smith PG, Eckhardt GS, (2013) Role of ubiquitin ligases and the proteasome in oncogenesis: novel targets for anticancer therapies. J Clin Oncol 31: 1231-1238
210. Chan CH, Morrow JK, Li CF, Gao Y, Jin G, Moten A, Stagg LJ, Ladbury JE, Cai Z, Xu D, et al (2013) Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression. Cell 154: 556-568
211. Chanet S, Schweisguth F, (2012) Regulation of epithelial polarity by the E3 ubiquitin ligase Neuralized and the Bearded inhibitors in Drosophila. Nat Cell Biol 14: 467-476
212. Benhra N, Vignaux F, Dussert A, Schweisguth F, Le Borgne R, (2010) Neuralized promotes basal to apical transcytosis of delta in epithelial cells. Mol Biol Cell 21: 2078-2086
213. Tenenhaus C, Subramaniam K, Dunn MA, Seydoux G, (2001) PIE-1 is a bifunctional protein that regulates maternal and zygotic gene expression in the embryonic germ line of Caenorhabditis elegans. Genes Dev 15: 1031-1040 (Pubitemid 32323552)
214. Tenlen JR, Molk JN, London N, Page BD, Priess JR, (2008) MEX-5 asymmetry in one-cell C. elegans embryos requires PAR-4- and PAR-1-dependent phosphorylation. Development 135: 3665-3675
215. Li S, Wang C, Sandanaraj E, Aw SS, Koe CT, Wong JJ, Yu F, Ang BT, Tang C, Wang H, (2014) The SCFSlimb E3 ligase complex regulates asymmetric division to inhibit neuroblast overgrowth. EMBO Rep 15: 165-174
216. Anon (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455: 1061-1068
217. Morais-de-Sá E, Vega-Rioja A, Trovisco V, St Johnston D, (2013) Oskar is targeted for degradation by the sequential action of Par-1, GSK-3, and the SCF-slimb ubiquitin ligase. Dev Cell 26: 303-314
218. Vertegaal AC, (2011) Uncovering ubiquitin and ubiquitin-like signaling networks. Chem Rev 111: 7923-7940
219. Choudhary C, Mann M, (2010) Decoding signalling networks by mass spectrometry-based proteomics. Nat Rev Mol Cell Biol 11: 427-439
220. Macek B, Mann M, Olsen JV, (2009) Global and site-specific quantitative phosphoproteomics: principles and applications. Annu Rev Pharmacol Toxicol 49: 199-221
221. Xu G, Paige JS, Jaffrey SR, (2010) Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling. Nat Biotechnol 28: 868-873
222. Kim TW, Guan S, Burlingame AL, Wang ZY, (2011) The CDG1 kinase mediates brassinosteroid signal transduction from BRI1 receptor kinase to BSU1 phosphatase and GSK3-like kinase BIN2. Mol Cell 43: 561-571
223. Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, Mann M, (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1: 376-386
224. Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, et al (2011) Global identification of modular cullin-RING ligase substrates. Cell 147: 459-474