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The Role of Tripartite Motif Family Proteins in TGF-β Signaling Pathway and Cancer

  • Lee, Ho-Jae (Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine)
  • Received : 2018.12.03
  • Accepted : 2018.12.18
  • Published : 2018.12.30

Abstract

$TGF-{\beta}$ signaling plays a tumor suppressive role in normal and premalignant cells but promotes tumor progression during the late stages of tumor development. The $TGF-{\beta}$ signaling pathway is tightly regulated at various levels, including transcriptional and post-translational mechanisms. Ubiquitination of signaling components, such as receptors and Smad proteins is one of the key regulatory mechanisms of $TGF-{\beta}$ signaling. Tripartite motif (TRIM) family of proteins is a highly conserved group of E3 ubiquitin ligase proteins that have been implicated in a variety of cellular functions, including cell growth, differentiation, immune response, and carcinogenesis. Recent emerging studies have shown that some TRIM family proteins function as important regulators in tumor initiation and progression. This review summarizes current knowledge of TRIM family proteins regulating the $TGF-{\beta}$ signaling pathway with relevance to cancer.

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

References

  1. Massague J. $TGF{\beta}$ signalling in context. Nat Rev Mol Cell Biol 2012;13:616-30. https://doi.org/10.1038/nrm3434
  2. Massague J, Blain SW, Lo RS. TGFbeta signaling in growth control, cancer, and heritable disorders. Cell 2000;103:295-309. https://doi.org/10.1016/S0092-8674(00)00121-5
  3. de Caestecker MP, Piek E, Roberts AB. Role of transforming growth factor-beta signaling in cancer. J Natl Cancer Inst 2000;92:1388-402. https://doi.org/10.1093/jnci/92.17.1388
  4. Principe DR, Doll JA, Bauer J, Jung B, Munshi HG, Bartholin L, et al. ${\beta}$: duality of function between tumor prevention and carcinogenesis. J Natl Cancer Inst 2014;106:djt369. https://doi.org/10.1093/jnci/djt369
  5. Katsuno Y, Lamouille S, Derynck R. TGB-${\beta}$ signaling and epithelial-mesenchymal transition in cancer progression. Curr Opin Oncol 2013;25:76-84. https://doi.org/10.1097/CCO.0b013e32835b6371
  6. Moustakas A, Heldin CH. The regulation of TGFbeta signal transduction. Development 2009;136:3699-714. https://doi.org/10.1242/dev.030338
  7. Lonn P, Moren A, Raja E, Dahl M, Moustakas A. Regulating the stability of TGFbeta receptors and Smads. Cell Res 2009;19:21-35. https://doi.org/10.1038/cr.2008.308
  8. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003;113:685-700. https://doi.org/10.1016/S0092-8674(03)00432-X
  9. Inoue Y, Imamura T. Regulation of TGF-beta family signaling by E3 ubiquitin ligases. Cancer Sci 2008;99:2107-12. https://doi.org/10.1111/j.1349-7006.2008.00925.x
  10. Crawford LJ, Johnston CK, Irvine AE. TRIM proteins in blood cancers. J Cell Commun Signal 2018;12:21-9. https://doi.org/10.1007/s12079-017-0423-5
  11. Napolitano LM, Meroni G. TRIM family: pleiotropy and diversification through homomultimer and heteromultimer formation. IUBMB Life 2012;64:64-71. https://doi.org/10.1002/iub.580
  12. Ozato K, Shin DM, Chang TH, Morse HC 3rd. TRIM family proteins and their emerging roles in innate immunity. Nat Rev Immunol 2008;8:849-60. https://doi.org/10.1038/nri2413
  13. Joazeiro CA, Weissman AM. RING finger proteins: mediators of ubiquitin ligase activity. Cell 2000;102:549-52. https://doi.org/10.1016/S0092-8674(00)00077-5
  14. Hatakeyama S. TRIM family proteins: roles in autophagy, immunity, and carcinogenesis. Trends Biochem Sci 2017;42:297-311. https://doi.org/10.1016/j.tibs.2017.01.002
  15. Hatakeyama S. TRIM proteins and cancer. Nat Rev Cancer 2011;11:792-804. https://doi.org/10.1038/nrc3139
  16. D'Cruz AA, Babon JJ, Norton RS, Nicola NA, Nicholson SE. Structure and function of the SPRY/B30.2 domain proteins involved in innate immunity. Protein Sci 2013;22:1-10.
  17. Aasland R, Gibson TJ, Stewart AF. The PHD finger: implications for chromatin-mediated transcriptional regulation. Trends Biochem Sci 1995;20:56-9. https://doi.org/10.1016/S0968-0004(00)88957-4
  18. Watanabe M, Hatakeyama S. TRIM proteins and diseases. J Biochem 2017;161:135-44.
  19. Kawai T, Akira S. Regulation of innate immune signalling pathways by the tripartite motif (TRIM) family proteins. EMBO Mol Med 2011;3:513-27. https://doi.org/10.1002/emmm.201100160
  20. Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem 1998;67:425-79. https://doi.org/10.1146/annurev.biochem.67.1.425
  21. Khetchoumian K, Teletin M, Mark M, Lerouge T, Cervino M, Oulad-Abdelghani M, et al. TIF1delta, a novel HP1-interacting member of the transcriptional intermediary factor 1 (TIF1) family expressed by elongating spermatids. J Biol Chem 2004;279:48329-41. https://doi.org/10.1074/jbc.M404779200
  22. Klugbauer S, Rabes HM. The transcription coactivator HTIF1 and a related protein are fused to the RET receptor tyrosine kinase in childhood papillary thyroid carcinomas. Oncogene 1999;18:4388-93. https://doi.org/10.1038/sj.onc.1202824
  23. Le Douarin B, Zechel C, Garnier JM, Lutz Y, Tora L, Pierrat P, et al. The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18. EMBO J 1995;14:2020-33. https://doi.org/10.1002/j.1460-2075.1995.tb07194.x
  24. Chambon M, Orsetti B, Berthe ML, Bascoul-Mollevi C, Rodriguez C, Duong V, et al. Prognostic significance of TRIM24/TIF-$1{\alpha}$ gene expression in breast cancer. Am J Pathol 2011;178:1461-9. https://doi.org/10.1016/j.ajpath.2010.12.026
  25. Khetchoumian K, Teletin M, Tisserand J, Mark M, Herquel B, Ignat M, et al. Loss of Trim24 (Tif1alpha) gene function confers oncogenic activity to retinoic acid receptor alpha. Nat Genet 2007;39:1500-6. https://doi.org/10.1038/ng.2007.15
  26. Joo HM, Kim JY, Jeong JB, Seong KM, Nam SY, Yang KH, et al. Ret finger protein 2 enhances ionizing radiation-induced apoptosis via degradation of AKT and MDM2. Eur J Cell Biol 2011;90:420-31. https://doi.org/10.1016/j.ejcb.2010.12.001
  27. Bernardi R, Scaglioni PP, Bergmann S, Horn HF, Vousden KH, Pandolfi PP. PML regulates p53 stability by sequestering Mdm2 to the nucleolus. Nat Cell Biol 2004;6:665-72. https://doi.org/10.1038/ncb1147
  28. Allton K, Jain AK, Herz HM, Tsai WW, Jung SY, Qin J, et al. Trim24 targets endogenous p53 for degradation. Proc Natl Acad Sci U S A 2009;106:11612-6. https://doi.org/10.1073/pnas.0813177106
  29. Wang C, Ivanov A, Chen L, Fredericks WJ, Seto E, Rauscher FJ 3rd, et al. MDM2 interaction with nuclear corepressor KAP1 contributes to p53 inactivation. EMBO J 2005;24:3279-90. https://doi.org/10.1038/sj.emboj.7600791
  30. Yuan Z, Villagra A, Peng L, Coppola D, Glozak M, Sotomayor EM, et al. The ATDC (TRIM29) protein binds p53 and antagonizes p53-mediated functions. Mol Cell Biol 2010;30:3004-15. https://doi.org/10.1128/MCB.01023-09
  31. Sho T, Tsukiyama T, Sato T, Kondo T, Cheng J, Saku T, et al. TRIM29 negatively regulates p53 via inhibition of Tip60. Biochim Biophys Acta 2011;1813:1245-53. https://doi.org/10.1016/j.bbamcr.2011.03.018
  32. Zhang L, Huang NJ, Chen C, Tang W, Kornbluth S. Ubiquitylation of p53 by the APC/C inhibitor Trim39. Proc Natl Acad Sci U S A 2012;109:20931-6. https://doi.org/10.1073/pnas.1212047110
  33. Zhao TT, Jin F, Li JG, Xu YY, Dong HT, Liu Q, et al. TRIM32 promotes proliferation and confers chemoresistance to breast cancer cells through activation of the NF-Κb pathway. J Cancer 2018;9:1349-56. https://doi.org/10.7150/jca.22390
  34. Wang C, Xu J, Fu H, Zhang Y, Zhang X, Yang D, et al. TRIM32 promotes cell proliferation and invasion by activating ${\beta}$-catenin signalling in gastric cancer. J Cell Mol Med 2018;22:5020-8. https://doi.org/10.1111/jcmm.13784
  35. Yin H, Li Z, Chen J, Hu X. Expression and the potential functions of TRIM32 in lung cancer tumorigenesis [published online ahead of print October 30, 2018]. J Cell Biochem. doi: 10.1002/jcb.27798.
  36. Miyazono K. Positive and negative regulation of TGF-beta signaling. J Cell Sci 2000;113:1101-9.
  37. Xu P, Lin X, Feng XH. Posttranslational regulation of Smads. Cold Spring Harb Perspect Biol 2016;8:a022087. https://doi.org/10.1101/cshperspect.a022087
  38. Xu P, Liu J, Derynck R. Post-translational regulation of $TGF-{\beta}$ receptor and Smad signaling. FEBS Lett 2012;586:1871-84. https://doi.org/10.1016/j.febslet.2012.05.010
  39. Massague J. TGFbeta in cancer. Cell 2008;134:215-30. https://doi.org/10.1016/j.cell.2008.07.001
  40. Dupont S, Zacchigna L, Cordenonsi M, Soligo S, Adorno M, Rugge M, et al. Germ-layer specification and control of cell growth by Ectodermin, a Smad4 ubiquitin ligase. Cell 2005;121:87-99. https://doi.org/10.1016/j.cell.2005.01.033
  41. Dupont S, Mamidi A, Cordenonsi M, Montagner M, Zacchigna L, Adorno M, et al. FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination. Cell 2009;136:123-35. https://doi.org/10.1016/j.cell.2008.10.051
  42. Zhao M, Mishra L, Deng CX. The role of $TGF-{\beta}$/SMAD4 signaling in cancer. Int J Biol Sci 2018;14:111-23. https://doi.org/10.7150/ijbs.23230
  43. Vincent DF, Yan KP, Treilleux I, Gay F, Arfi V, Kaniewski B, et al. Inactivation of TIF1gamma cooperates with Kras to induce cystic tumors of the pancreas. PLoS Genet 2009;5:e1000575. https://doi.org/10.1371/journal.pgen.1000575
  44. He W, Dorn DC, Erdjument-Bromage H, Tempst P, Moore MA, Massague J. Hematopoiesis controlled by distinct TIF1gamma and Smad4 branches of the TGFbeta pathway. Cell 2006;125:929-41. https://doi.org/10.1016/j.cell.2006.03.045
  45. Ruthenburg AJ, Li H, Patel DJ, Allis CD. Multivalent engagement of chromatin modifications by linked binding modules. Nat Rev Mol Cell Biol 2007;8:983-94. https://doi.org/10.1038/nrm2298
  46. Agricola E, Randall RA, Gaarenstroom T, Dupont S, Hill CS. Recruitment of $TIF1{\gamma}$ to chromatin via its PHD finger-bromodomain activates its ubiquitin ligase and transcriptional repressor activities. Mol Cell 2011;43:85-96. https://doi.org/10.1016/j.molcel.2011.05.020
  47. Gaarenstroom T, Hill CS. $TGF-{\beta}$ signaling to chromatin: how Smads regulate transcription during self-renewal and differentiation. Semin Cell Dev Biol 2014;32:107-18. https://doi.org/10.1016/j.semcdb.2014.01.009
  48. Xi Q, Wang Z, Zaromytidou AI, Zhang XH, Chow-Tsang LF, Liu JX, et al. A poised chromatin platform for $TGF-{\beta}$ access to master regulators. Cell 2011;147:1511-24. https://doi.org/10.1016/j.cell.2011.11.032
  49. Bagchi A, Mills AA. The quest for the 1p36 tumor suppressor. Cancer Res 2008;68:2551-6. https://doi.org/10.1158/0008-5472.CAN-07-2095
  50. Lott ST, Chen N, Chandler DS, Yang Q, Wang L, Rodriguez M, et al. DEAR1 is a dominant regulator of acinar morphogenesis and an independent predictor of local recurrence-free survival in early-onset breast cancer. PLoS Med 2009;6:e1000068. https://doi.org/10.1371/journal.pmed.1000068
  51. Imamura T, Hikita A, Inoue Y. The roles of $TGF-{\beta}$ signaling in carcinogenesis and breast cancer metastasis. Breast Cancer 2012;19:118-24. https://doi.org/10.1007/s12282-011-0321-2
  52. Huang F, Xiao H, Sun BL, Yang RG. Characterization of TRIM62 as a RING finger E3 ubiquitin ligase and its subcellular localization. Biochem Biophys Res Commun 2013;432:208-13. https://doi.org/10.1016/j.bbrc.2013.02.012
  53. Chen N, Balasenthil S, Reuther J, Killary AM. DEAR1, a novel tumor suppressor that regulates cell polarity and epithelial plasticity. Cancer Res 2014;74:5683-9. https://doi.org/10.1158/0008-5472.CAN-14-1171
  54. Quintas-Cardama A, Zhang N, Qiu YH, Post S, Creighton CJ, Cortes J, et al. Loss of TRIM62 expression is an independent adverse prognostic factor in acute myeloid leukemia. Clin Lymphoma Myeloma Leuk 2015;15:115-27.e15. https://doi.org/10.1016/j.clml.2014.07.011
  55. Quintas-Cardama A, Post SM, Solis LM, Xiong S, Yang P, Chen N, et al. Loss of the novel tumour suppressor and polarity gene Trim62 (Dear1) synergizes with oncogenic Ras in invasive lung cancer. J Pathol 2014;234:108-19. https://doi.org/10.1002/path.4385
  56. Chen N, Balasenthil S, Reuther J, Frayna A, Wang Y, Chandler DS, et al. DEAR1 is a chromosome 1p35 tumor suppressor and master regulator of $TGF-{\beta}$-driven epithelial-mesenchymal transition. Cancer Discov 2013;3:1172-89. https://doi.org/10.1158/2159-8290.CD-12-0499
  57. Wang X, Shi W, Shi H, Lu S, Wang K, Sun C, et al. TRIM11 overexpression promotes proliferation, migration and invasion of lung cancer cells. J Exp Clin Cancer Res 2016;35:100. https://doi.org/10.1186/s13046-016-0379-y
  58. Di K, Linskey ME, Bota DA. TRIM11 is overexpressed in high-grade gliomas and promotes proliferation, invasion, migration and glial tumor growth. Oncogene 2013;32:5038-47. https://doi.org/10.1038/onc.2012.531
  59. Ishikawa H, Tachikawa H, Miura Y, Takahashi N. TRIM11 binds to and destabilizes a key component of the activator-mediated cofactor complex (ARC105) through the ubiquitin-proteasome system. FEBS Lett 2006;580:4784-92. https://doi.org/10.1016/j.febslet.2006.07.066
  60. Mittler G, Kremmer E, Timmers HT, Meisterernst M. Novel critical role of a human Mediator complex for basal RNA polymerase II transcription. EMBO Rep 2001;2:808-13. https://doi.org/10.1093/embo-reports/kve186
  61. Naar AM, Beaurang PA, Zhou S, Abraham S, Solomon W, Tjian R. Composite co-activator ARC mediates chromatin-directed transcriptional activation. Nature 1999;398:828-32. https://doi.org/10.1038/19789
  62. Kato Y, Habas R, Katsuyama Y, Naar AM, He X. A component of the ARC/Mediator complex required for TGF beta/Nodal signalling. Nature 2002;418:641-6. https://doi.org/10.1038/nature00969
  63. Zhao M, Yang X, Fu Y, Wang H, Ning Y, Yan J, et al. Mediator MED15 modulates transforming growth factor beta ($TGF{\beta}$)/Smad signaling and breast cancer cell metastasis. J Mol Cell Biol 2013;5:57-60. https://doi.org/10.1093/jmcb/mjs054
  64. Inoue S, Orimo A, Hosoi T, Kondo S, Toyoshima H, Kondo T, et al. Genomic binding-site cloning reveals an estrogen-responsive gene that encodes a RING finger protein. Proc Natl Acad Sci U S A 1993;90:11117-21. https://doi.org/10.1073/pnas.90.23.11117
  65. Sun N, Xue Y, Dai T, Li X, Zheng N. Tripartite motif containing 25 promotes proliferation and invasion of colorectal cancer cells through $TGF-{\beta}$ signaling. Biosci Rep 2017;37:BSR20170805. https://doi.org/10.1042/BSR20170805
  66. Zhu Z, Wang Y, Zhang C, Yu S, Zhu Q, Hou K, et al. TRIM25 blockade by RNA interference inhibited migration and invasion of gastric cancer cells through $TGF-{\beta}$ signaling. Sci Rep 2016;6:19070. https://doi.org/10.1038/srep19070
  67. Nakagawa T, Hosogane M, Nakagawa M, Morohoshi A, Funayama R, Nakayama K. Transforming growth factor ${\beta}$-induced proliferative arrest mediated by TRIM26-dependent TAF7 degradation and its antagonism by MYC. Mol Cell Biol 2018;38:e00449-17.
  68. Chen L, Munoz-Antonia T, Cress WD. Trim28 contributes to EMT via regulation of E-cadherin and N-cadherin in lung cancer cell lines. PLoS One 2014;9:e101040. https://doi.org/10.1371/journal.pone.0101040
  69. Deng B, Zhang S, Zhang Y, Miao Y, Meng X, Guo K. Knockdown of tripartite motif containing 28 suppresses the migration, invasion and epithelial-mesenchymal transition in ovarian carcinoma cells through down-regulation of Wnt/${\beta}$-catenin signaling pathway. Neoplasma 2017;64:893-900. https://doi.org/10.4149/neo_2017_611
  70. Wei C, Cheng J, Zhou B, Zhu L, Khan MA, He T, et al. Tripartite motif containing 28 (TRIM28) promotes breast cancer metastasis by stabilizing TWIST1 protein. Sci Rep 2016;6:29822. https://doi.org/10.1038/srep29822
  71. Chen Y, Guo Y, Yang H, Shi G, Xu G, Shi J, et al. TRIM66 overexpression contributes to osteosarcoma carcinogenesis and indicates poor survival outcome. Oncotarget 2015;6:23708-19.
  72. Liu Y, Dong Y, Zhao L, Su L, Diao K, Mi X. TRIM59 overexpression correlates with poor prognosis and contributes to breast cancer progression through AKT signaling pathway. Mol Carcinog 2018;57:1792-802. https://doi.org/10.1002/mc.22897
  73. Zhan W, Han T, Zhang C, Xie C, Gan M, Deng K, et al. TRIM59 promotes the proliferation and migration of non-small cell lung cancer cells by upregulating cell cycle related proteins. PLoS One 2015;10:e0142596. https://doi.org/10.1371/journal.pone.0142596
  74. Zhou Z, Ji Z, Wang Y, Li J, Cao H, Zhu HH, et al. TRIM59 is up-regulated in gastric tumors, promoting ubiquitination and degradation of p53. Gastroenterology 2014;147:1043-54. https://doi.org/10.1053/j.gastro.2014.07.021
  75. Chen W, Zhao K, Miao C, Xu A, Zhang J, Zhu J, et al. Silencing Trim59 inhibits invasion/migration and epithelial-to-mesenchymal transition via $TGF-{\beta}$/Smad2/3 signaling pathway in bladder cancer cells. Onco Targets Ther 2017;10:1503-12. https://doi.org/10.2147/OTT.S130139
  76. Zhang Y, Yang WB. Down-regulation of tripartite motif protein 59 inhibits proliferation, migration and invasion in breast cancer cells. Biomed Pharmacother 2017;89:462-7. https://doi.org/10.1016/j.biopha.2017.02.039
  77. Cai C, Masumiya H, Weisleder N, Matsuda N, Nishi M, Hwang M, et al. MG53 nucleates assembly of cell membrane repair machinery. Nat Cell Biol 2009;11:56-64. https://doi.org/10.1038/ncb1812
  78. Zhao J, Lei H. Tripartite motif protein 72 regulates the proliferation and migration of rat cardiac fibroblasts via the transforming growth factor-${\beta}$ signaling pathway. Cardiology 2016;134:340-6. https://doi.org/10.1159/000443703
  79. Li H, Duann P, Lin PH, Zhao L, Fan Z, Tan T, et al. Modulation of wound healing and scar formation by MG53 protein-mediated cell membrane repair. J Biol Chem 2015;290:24592-603. https://doi.org/10.1074/jbc.M115.680074