Ski and SnoN, potent negative regulators of TGF-β signaling

Cell Research

Volumn 19, Issue 1, 2009, Pages 47-57

  Deheuninck, Julien ^a   Luo, Kunxin ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Development; Senescence; Signal transduction; Ski; SnoN; TGF signaling; Tumorigenesis

Indexed keywords

DNA BINDING PROTEIN; ONCOPROTEIN; SIGNAL PEPTIDE; SKI PROTEIN, HUMAN; SKIL PROTEIN, HUMAN; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR;

ANIMAL; CHICKEN; DRUG ANTAGONISM; EMBRYO DEVELOPMENT; HUMAN; METABOLISM; NEOPLASM; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; CHICKENS; DNA-BINDING PROTEINS; EMBRYONIC DEVELOPMENT; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; NEOPLASMS; PROTO-ONCOGENE PROTEINS; RECEPTORS, TRANSFORMING GROWTH FACTOR BETA; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA;

EID: 58149239731     PISSN: 10010602     EISSN: 17487838     Source Type: Journal    
DOI: 10.1038/cr.2008.324     Document Type: Review

References (116)

1. Li Y, Turck CM, Teumer JK, Stavnezer E. Unique sequence, ski, in Sloan-Kettering avian retroviruses with properties of a new cell-derived oncogene. J Virol 1986; 57:1065-1072.
2. Nomura N, Sasamoto S, Ishii S, Date T, Matsui M, Ishizaki R. Isolation of human cDNA clones of ski and the ski-related gene, sno. Nucleic Acids Res 1989; 17:5489-5500.
3. Pearson-White S, Crittenden R. Proto-oncogene sno expression, alternative isoforms and immediate early serum response. Nucleic Acids Res 1997; 25:2930-2937.
4. Pelzer T, Lyons GE, Kim S, Moreadith RW. Cloning and characterization of the murine homolog of the sno protooncogene reveals a novel splice variant. Dev Dyn 1996; 205:114-125.
5. Pearson-White S. SnoI, a novel alternatively spliced isoform of the ski protooncogene homolog, sno. Nucleic Acids Res 1993; 21:4632-4638.
6. Arndt S, Poser I, Schubert T, Moser M, Bosserhoff AK. Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues. Lab Invest; J Tech Methods Pathol 2005; 85:1330-1341.
7. Arndt S, Poser I, Moser M, Bosserhoff AK. Fussel-15, a novel Ski/Sno homolog protein, antagonizes BMP signaling. Mol Cell Neurosci 2007; 34:603-611.
8. Kozmik Z, Pfeffer P, Kralova J, et al. Molecular cloning and expression of the human and mouse homologues of the Drosophila dachshund gene. Dev Genes Evol 1999; 209:537-545.
9. Wu K, Yang Y, Wang C, et al. DACH1 inhibits transforming growth factor-beta signaling through binding Smad4. J Biol Chem 2003; 278:51673-51684.
10. Wu JW, Krawitz AR, Chai J, et al. Structural mechanism of Smad4 recognition by the nuclear oncoprotein Ski: insights on Ski-mediated repression of TGF-beta signaling. Cell 2002; 111:357-367.
11. Wilson JJ, Malakhova M, Zhang R, Joachimiak A, Hegde RS. Crystal structure of the dachshund homology domain of human SKI. Structure 2004; 12:785-792.
12. Nomura T, Khan MM, Kaul SC, et al. Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor. Genes Dev 1999; 13:412-423.
13. Heyman HC, Stavnezer E. A carboxyl-terminal region of the ski oncoprotein mediates homodimerization as well as heterodimerization with the related protein SnoN. J Biol Chem 1994; 269:26996-27003.
14. Cohen SB, Zheng G, Heyman HC, Stavnezer E. Heterodimers of the SnoN and Ski oncoproteins form preferentially over homodimers and are more potent transforming agents. Nucleic Acids Res 1999; 27:1006-1014.
15. Kaufman CD, Martinez-Rodriguez G, Hackett PB Jr. Ectopic expression of c-ski disrupts gastrulation and neural patterning in zebrafish. Mech Dev 2000; 95:147-162.
16. Berk M, Desai SY, Heyman HC, Colmenares C. Mice lacking the ski proto-oncogene have defects in neurulation, craniofacial, patterning, and skeletal muscle development. Genes Dev 1997; 11:2029-2039.
17. Amaravadi LS, Neff AW, Sleeman JP, Smith RC. Autonomous neural axis formation by ectopic expression of the protooncogene c-ski. Dev Biol 1997; 192:392-404.
18. Sleeman JP, Laskey RA. Xenopus c-ski contains a novel coiled-coil protein domain, and is maternally expressed during development. Oncogene 1993; 8:67-77.
19. Lyons GE, Micales BK, Herr MJ, et al. Protooncogene c-ski is expressed in both proliferating and postmitotic neuronal populations. Dev Dyn 1994; 201:354-365.
20. Namciu S, Lyons GE, Micales BK, Heyman HC, Colmenares C, Stavnezer E. Enhanced expression of mouse c-ski accompanies terminal skeletal muscle differentiation in vivo and in vitro. Dev Dyn 1995; 204:291-300.
21. Gajecka M, Mackay KL, Shaffer LG. Monosomy 1p36 deletion syndrome. Am J Med Genet 2007; 145C:346-356.
22. Colmenares C, Heilstedt HA, Shaffer LG, et al. Loss of the SKI proto-oncogene in individuals affected with 1p36 deletion syndrome is predicted by strain-dependent defects in Ski-/- mice. Nat Genet 2002; 30:106-109.
23. Shinagawa T, Dong HD, Xu M, Maekawa T, Ishii S. The sno gene, which encodes a component of the histone deacetylase complex, acts as a tumor suppressor in mice. EMBO J 2000; 19:2280-2291.
24. Pearson-White S, McDuffie M. Defective T-cell activation is associated with augmented transforming growth factor Beta sensitivity in mice with mutations in the Sno gene. Mol Cell Biol 2003; 23:5446-5459.
25. Boyer PL, Colmenares C, Stavnezer E, Hughes SH. Sequence and biological activity of chicken snoN cDNA clones. Oncogene 1993; 8:457-466.
26. Colmenares C, Stavnezer E. The ski oncogene induces muscle differentiation in quail embryo cells. Cell 1989; 59:293-303.
27. Sutrave P, Kelly AM, Hughes SH. Ski can cause selective growth of skeletal muscle in transgenic mice. Genes Dev 1990; 4:1462-1472.
28. Kobayashi N, Goto K, Horiguchi K, et al. c-Ski activates MyoD in the nucleus of myoblastic cells through suppression of histone deacetylases. Genes Cells 2007; 12:375-385.
29. Mimura N, Ichikawa K, Asano A, Nagase T, Ishii S. A transient increase of snoN transcript by growth arrest upon serum deprivation and cell-to-cell contact. FEBS Lett 1996; 397:253-259.
30. Stegmuller J, Konishi Y, Huynh MA, Yuan Z, Dibacco S, Bonni A. Cell-intrinsic regulation of axonal morphogenesis by the Cdh1-APC target SnoN. Neuron 2006; 50:389-400.
31. Atanasoski S, Notterpek L, Lee HY, et al. The protooncogene Ski controls Schwann cell proliferation and myelination. Neuron 2004; 43:499-511.
32. Dahl R, Kieslinger M, Beug H, Hayman MJ. Transformation of hematopoietic cells by the Ski oncoprotein involves repression of retinoic acid receptor signaling. Proc Natl Acad Sci USA 1998; 95:11187-11192.
33. Pearson-White S, Deacon D, Crittenden R, et al. The ski/sno protooncogene family in hematopoietic development. Blood 1995; 86:2146-2155.
34. Liu X, Zhang E, Li P, et al. Expression and possible mechanism of c-ski, a novel tissue repair-related gene during normal and radiation-impaired wound healing. Wound Repair Regen 2006; 14:162-171.
35. Macias-Silva M, Li W, Leu JI, Crissey MA, Taub R. Upregulated transcriptional repressors SnoN and Ski bind Smad proteins to antagonize transforming growth factor-beta signals during liver regeneration. J Biol Chem 2002; 277:28483-28490.
36. Tan R, Zhang J, Tan X, Zhang X, Yang J, Liu Y. Downregulation of SnoN expression in obstructive nephropathy is mediated by an enhanced ubiquitin-dependent degradation. J Am Soc Nephrol 2006; 17:2781-2791.
37. Fukasawa H, Yamamoto T, Togawa A, et al. Ubiquitin-dependent degradation of SnoN and Ski is increased in renal fibrosis induced by obstructive injury. Kidney Int 2006; 69:1733-1740.
38. Colmenares C, Sutrave P, Hughes SH, Stavnezer E. Activation of the c-ski oncogene by overexpression. J Virol 1991; 65:4929-4935.
39. Imoto I, Pimkhaokham A, Fukuda Y, et al. SNO is a probable target for gene amplification at 3q26 in squamous-cell carcinomas of the esophagus. Biochem Biophys Res Commun 2001; 286:559-565.
40. Fukuchi M, Nakajima M, Fukai Y, et al. Increased expression of c-Ski as a co-repressor in transforming growth factor-beta signaling correlates with progression of esophageal squamous cell carcinoma. Int J Cancer 2004; 108:818-824.
41. Akagi I, Miyashita M, Makino H, et al. SnoN overexpression is predictive of poor survival in patients with esophageal squamous cell carcinoma. Ann Surg Oncol 2008; 15:2965-2975
42. Poser I, Rothhammer T, Dooley S, Weiskirchen R, Bosserhoff AK. Characterization of Sno expression in malignant melanoma. Int J Oncol 2005; 26:1411-1417.
43. Reed JA, Lin Q, Chen D, Mian IS, Medrano EE. SKI pathways inducing progression of human melanoma. Cancer Metastasis Rev 2005; 24:265-272.
44. Chen D, Xu W, Bales E, et al. SKI activates Wnt/beta-catenin signaling in human melanoma. Cancer Res 2003; 63:6626-6634.
45. Zhang F, Lundin M, Ristimaki A, et al. Ski-related novel protein N (SnoN), a negative controller of transforming growth factor-beta signaling, is a prognostic marker in estrogen receptor-positive breast carcinomas. Cancer Res 2003; 63:5005-5010.
46. Buess M, Terracciano L, Reuter J, et al. Amplification of SKI is a prognostic marker in early colorectal cancer. Neoplasia (New York, NY) 2004; 6:207-212.
47. Ritter M, Kattmann D, Teichler S, et al. Inhibition of retinoic acid receptor signaling by Ski in acute myeloid leukemia. Leukemia 2006; 20:437-443.
48. Racz A, Brass N, Heckel D, Pahl S, Remberger K, Meese E. Expression analysis of genes at 3q26-q27 involved in frequent amplification in squamous cell lung carcinoma. Eur J Cancer 1999; 35:641-646.
49. Sugita M, Tanaka N, Davidson S, et al. Molecular definition of a small amplification domain within 3q26 in tumors of cervix, ovary, and lung. Cancer Genet Cytogenet 2000; 117:9-18.
50. Singh B, Gogineni SK, Sacks PG, et al. Molecular cytogenetic characterization of head and neck squamous cell carcinoma and refinement of 3q amplification. Cancer Res 2001; 61:4506-4513.
51. Lin SC, Liu CJ, Ko SY, Chang HC, Liu TY, Chang KW. Copy number amplification of 3q26-27 oncogenes in microdissected oral squamous cell carcinoma and oral brushed samples from areca chewers. J Pathol 2005; 206:417-422.
52. Hopman AH, Theelen W, Hommelberg PP, et al. Genomic integration of oncogenic HPV and gain of the human telomerase gene TERC at 3q26 are strongly associated events in the progression of uterine cervical dysplasia to invasive cancer. J Pathol 2006; 210:412-419.
53. Nanjundan M, Nakayama Y, Cheng KW, et al. Amplification of MDS1/EVI1 and EVI1, located in the 3q26.2 amplicon, is associated with favorable patient prognosis in ovarian cancer. Cancer Res 2007; 67:3074-3084.
54. Jung V, Kindich R, Kamradt J, et al. Genomic and expression analysis of the 3q25-q26 amplification unit reveals TLOC1/SEC62 as a probable target gene in prostate cancer. Mol Cancer Res 2006; 4:169-176.
55. Zhu Q, Krakowski AR, Dunham EE, et al. Dual role of SnoN in mammalian tumorigenesis. Mol Cell Biol 2007; 27:324-339.
56. Heider TR, Lyman S, Schoonhoven R, Behrns KE. Ski promotes tumor growth through abrogation of transforming growth factor-beta signaling in pancreatic cancer. Ann Surg 2007; 246:61-68.
57. Villanacci V, Bellone G, Battaglia E, et al. Ski/SnoN expression in the sequence metaplasia-dysplasia-adenocarcinoma of Barrett's esophagus. Hum Pathol 2008; 39:403-409.
58. Chia JA, Simms LA, Cozzi SJ, et al. SnoN expression is differently regulated in microsatellite unstable compared with microsatellite stable colorectal cancers. BMC Cancer 2006; 6:252.
59. Shinagawa T, Nomura T, Colmenares C, Ohira M, Nakagawara A, Ishii S. Increased susceptibility to tumorigenesis of ski-deficient heterozygous mice. Oncogene 2001; 20:8100-8108.
60. Pan D, Zhu Q, Luo K. SnoN functions as a tumor suppressor by inducing premature senescence. Submitted.
61. Ramel MC, Emery CM, Foulger R, Goberdhan DC, van den Heuvel M, Wilson C. Drosophila SnoN modulates growth and patterning by antagonizing TGF-beta signalling. Mech Dev 2007; 124:304-317.
62. Le Scolan E, Zhu Q, Wang L, et al. Transforming growth factor-beta suppresses the ability of Ski to inhibit tumor metastasis by inducing its degradation. Cancer Res 2008; 68:3277-3285.
63. Stroschein SL, Wang W, Zhou S, Zhou Q, Luo K. Negative feedback regulation of TGF-beta signaling by the SnoN oncoprotein. Science (New York, NY) 1999; 286:771-774.
64. Luo K, Stroschein SL, Wang W, et al. The Ski oncoprotein interacts with the Smad proteins to repress TGFbeta signaling. Genes Dev 1999; 13:2196-2206.
65. Tokitou F, Nomura T, Khan MM, et al. Viral ski inhibits retinoblastoma protein (Rb)-mediated transcriptional repression in a dominant negative fashion. J Biol Chem 1999; 274:4485-4488.
66. Ueki N, Zhang L, Hayman MJ. Ski negatively regulates erythroid differentiation through its interaction with GATA1. Mol Cell Biol 2004; 24:10118-10125.
67. Dai P, Shinagawa T, Nomura T, et al. Ski is involved in transcriptional regulation by the repressor and full-length forms of Gli3. Genes Dev 2002; 16:2843-2848.
68. Karagianni P, Wong J. HDAC3: taking the SMRT-N-CoRrect road to repression. Oncogene 2007; 26:5439-5449.
69. Luo K. Ski and SnoN: negative regulators of TGF-beta signaling. Curr Opin Genet Dev 2004; 14:65-70.
70. Suzuki H, Yagi K, Kondo M, Kato M, Miyazono K, Miyazawa K. c-Ski inhibits the TGF-beta signaling pathway through stabilization of inactive Smad complexes on Smad-binding elements. Oncogene 2004; 23:5068-5076.
71. Ueki N, Hayman MJ. Direct interaction of Ski with either Smad3 or Smad4 is necessary and sufficient for Ski-mediated repression of transforming growth factor-beta signaling. J Biol Chem 2003; 278:32489-32492.
72. Chen W, Lam SS, Srinath H, Schiffer CA, Royer WE Jr., Lin K. Competition between Ski and CREB-binding protein for binding to Smad proteins in transforming growth factor-beta signaling. J Biol Chem 2007; 282:11365-11376.
73. Akiyoshi S, Inoue H, Hanai J, et al. c-Ski acts as a transcriptional co-repressor in transforming growth factor-beta signaling through interaction with smads. J Biol Chem 1999; 274:35269-35277.
74. Prunier C, Pessah M, Ferrand N, Seo SR, Howe P, Atfi A. The oncoprotein Ski acts as an antagonist of transforming growth factor-beta signaling by suppressing Smad2 phosphorylation. J Biol Chem 2003; 278:26249- 26257.
75. Sarker KP, Wilson SM, Bonni S. SnoN is a cell type-specific mediator of transforming growth factor-beta responses. J Biol Chem 2005; 280:13037-13046.
76. He J, Tegen SB, Krawitz AR, Martin GS, Luo K. The transforming activity of Ski and SnoN is dependent on their ability to repress the activity of Smad proteins. J Biol Chem 2003; 278:30540-30547.
77. Takeda M, Mizuide M, Oka M, et al. Interaction with Smad4 is indispensable for suppression of BMP signaling by c-Ski. Mol Biol Cell 2004; 15:963-972.
78. Wang W, Mariani FV, Harland RM, Luo K. Ski represses bone morphogenic protein signaling in Xenopus and mammalian cells. Proc Natl Acad Sci USA 2000; 97:14394-14399.
79. Winograd J, Reilly MP, Roe R, et al. Perinatal lethality and multiple craniofacial malformations in MSX2 transgenic mice. Hum Mol Genet 1997; 6:369-379.
80. Barlow AJ, Francis-West PH. Ectopic application of recombinant BMP-2 and BMP-4 can change patterning of developing chick facial primordia. Development (Cambridge, England) 1997; 124:391-398.
81. Sarker KP, Kataoka H, Chan A, et al. ING2 as a novel mediator of transforming growth factor-beta-dependent responses in epithelial cells. J Biol Chem 2008; 283:13269-13279.
82. Ueki N, Hayman MJ. Signal-dependent N-CoR requirement for repression by the Ski oncoprotein. J Biol Chem 2003; 278:24858-24864.
83. Khan MM, Nomura T, Kim H, et al. Role of PML and PML-RARalpha in Mad-mediated transcriptional repression. Mol Cell 2001; 7:1233-1243.
84. Harada J, Kokura K, Kanei-Ishii C, et al. Requirement of the co-repressor homeodomain-interacting protein kinase 2 for ski-mediated inhibition of bone morphogenetic protein-induced transcriptional activation. J Biol Chem 2003; 278:38998-39005.
85. Kokura K, Kaul SC, Wadhwa R, et al. The Ski protein family is required for MeCP2-mediated transcriptional repression. J Biol Chem 2001; 276:34115-34121.
86. Ueki N, Zhang L, Hayman MJ. Ski can negatively regulates macrophage differentiation through its interaction with PU.1. Oncogene 2008; 27:300-307.
87. Jacob C, Grabner H, Atanasoski S, Suter U. Expression and localization of Ski determine cell type-specific TGFbeta signaling effects on the cell cycle. J Cell Biol 2008; 182:519-530.
88. Dahl R, Wani B, Hayman MJ. The Ski oncoprotein interacts with Skip, the human homolog of Drosophila Bx42. Oncogene 1998; 16:1579-1586.
89. Leong GM, Subramaniam N, Figueroa J, et al. Ski-interacting protein interacts with Smad proteins to augment transforming growth factor-beta-dependent transcription. J Biol Chem 2001; 276:18243-18248.
90. Prathapam T, Kuhne C, Banks L. Skip interacts with the retinoblastoma tumor suppressor and inhibits its transcriptional repression activity. Nucleic Acids Res 2002; 30:5261-5268.
91. Wilkinson DS, Ogden SK, Stratton SA, et al. A direct intersection between p53 and transforming growth factor beta pathways targets chromatin modification and transcription repression of the alpha-fetoprotein gene. Mol Cell Biol 2005; 25:1200-1212.
92. Zhu Q, Pearson-White S, Luo K. Requirement for the SnoN oncoprotein in transforming growth factor beta-induced oncogenic transformation of fibroblast cells. Mol Cell Biol 2005; 25:10731-10744.
93. Yang J, Dai C, Liu Y. A novel mechanism by which hepatocyte growth factor blocks tubular epithelial to mesenchymal transition. J Am Soc Nephrol 2005; 16:68-78.
94. Tan R, Zhang X, Yang J, Li Y, Liu Y. Molecular basis for the cell type specific induction of SnoN expression by hepatocyte growth factor. J Am Soc Nephrol 2007; 18:2340-2349.
95. Dai C, Liu Y. Hepatocyte growth factor antagonizes the profibrotic action of TGF-beta1 in mesangial cells by stabilizing Smad transcriptional corepressor TGIF. J Am Soc Nephrol 2004; 15:1402-1412.
96. Liu X, Li P, Liu P, et al. The essential role for c-Ski in mediating TGF-beta1-induced bi-directional effects on skin fibroblast proliferation through a feedback loop. Biochem J 2008; 409:289-297.
97. Sun Y, Liu X, Ng-Eaton E, Lodish HF, Weinberg RA. SnoN and Ski protooncoproteins are rapidly degraded in response to transforming growth factor beta signaling. Proc Natl Acad Sci USA 1999; 96:12442-12447.
98. Bonni S, Wang HR, Causing CG, et al. TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that tarncer Res 2005; 65:4782-4788.
99. Wan Y, Liu X, Kirschner MW. The anaphase-promoting complex mediates TGF-beta signaling by targeting SnoN for destruction. Mol Cell 2001; 8:1027-1039.
100. Stroschein SL, Bonni S, Wrana JL, Luo K. Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN. Genes Dev 2001; 15:2822-2836.
101. Wu G, Glickstein S, Liu W, et al. The anaphase-promoting complex coordinates initiation of lens differentiation. Mol Biol Cell 2007; 18:1018-1029.
102. Nagano Y, Mavrakis KJ, Lee KL, et al. Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth factor-beta signaling. J Biol Chem 2007; 282:20492-20501.
103. Levy L, Howell M, Das D, Harkin S, Episkopou V, Hill CS. Arkadia activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation. Mol Cell Biol 2007; 27:6068-6083.
104. Edmiston JS, Yeudall WA, Chung TD, Lebman DA. Inability of transforming growth factor-beta to cause SnoN degradation leads to resistance to transforming growth factor-beta-induced growth arrest in esophageal cancer cells. Cancer Res 2005; 65:4782-4788.
105. Stegmuller J, Huynh MA, Yuan Z, Konishi Y, Bonni A. TGFbeta-Smad2 signaling regulates the Cdh1-APC/SnoN pathway of axonal morphogenesis. J Neurosci 2008; 28:1961-1969.
106. Baldwin RL, Tran H, Karlan BY. Loss of c-myc repression coincides with ovarian cancer resistance to transforming growth factor beta growth arrest independent of transforming growth factor beta/Smad signaling. Cancer Res 2003; 63:1413-1419.
107. Macdonald M, Wan Y, Wang W, et al. Control of cell cycle-dependent degradation of c-Ski proto-oncoprotein by Cdc34. Oncogene 2004; 23:5643-5653.
108. Marcelain K, Hayman MJ. The Ski oncoprotein is upregulated and localized at the centrosomes and mitotic spindle during mitosis. Oncogene 2005; 24:4321-4329.
109. Wrighton KH, Liang M, Bryan B, et al. Transforming growth factor-beta-independent regulation of myogenesis by SnoN sumoylation. J Biol Chem 2007; 282:6517-6524.
110. Hsu YH, Sarker KP, Pot I, Chan A, Netherton SJ, Bonni S. Sumoylated SnoN represses transcription in a promoter-specific manner. J Biol Chem 2006; 281:33008-33018.
111. Kajino T, Omori E, Ishii S, Matsumoto K, Ninomiya-Tsuji J. TAK1 MAPK kinase kinase mediates transforming growth factor-beta signaling by targeting SnoN oncoprotein for degradation. J Biol Chem 2007; 282:9475-9481.
112. Sutrave P, Copeland TD, Showalter SD, Hughes SH. Characterization of chicken c-ski oncogene products expressed by retrovirus vectors. Mol Cell Biol 1990; 10:3137-3144.
113. Krakowski AR, Laboureau J, Mauviel A, Bissell MJ, Luo K. Cytoplasmic SnoN in normal tissues and nonmalignant cells antagonizes TGF-beta signaling by sequestration of the Smad proteins. Proc Natl Acad Sci USA 2005; 102:12437-12442.
114. Reed JA, Bales E, Xu W, Okan NA, Bandyopadhyay D, Medrano EE. Cytoplasmic localization of the oncogenic protein Ski in human cutaneous melanomas in vivo: functional implications for transforming growth factor beta signaling. Cancer Res 2001; 61:8074-8078.
115. Nagata M, Goto K, Ehata S, et al. Nuclear and cytoplasmic c-Ski differently modulate cellular functions. Genes Cells 2006; 11:1267-1280.
116. Kokura K, Kim H, Shinagawa T, Khan MM, Nomura T, Ishii S. The Ski-binding protein C184M negatively regulates tumor growth factor-beta signaling by sequestering the Smad proteins in the cytoplasm. J Biol Chem 2003; 278:20133-20139.