Key role for ubiquitin protein modification in TGFβ signal transduction.

Upsala Journal of Medical Sciences
Miriam De Boeck, Peter ten Dijke

Abstract

The transforming growth factor β (TGFβ) superfamily of signal transduction molecules plays crucial roles in the regulation of cell behavior. TGFβ regulates gene transcription through Smad proteins and signals via non-Smad pathways. The TGFβ pathway is strictly regulated, and perturbations lead to tumorigenesis. Several pathway components are known to be targeted for proteasomal degradation via ubiquitination by E3 ligases. Smurfs are well known negative regulators of TGFβ, which function as E3 ligases recruited by adaptors such as I-Smads. TGFβ signaling can also be enhanced by E3 ligases, such as Arkadia, that target repressors for degradation. It is becoming clear that E3 ligases often target multiple pathways, thereby acting as mediators of signaling cross-talk. Regulation via ubiquitination involves a complex network of E3 ligases, adaptor proteins, and deubiquitinating enzymes (DUBs), the last-mentioned acting by removing ubiquitin from its targets. Interestingly, also non-degradative ubiquitin modifications are known to play important roles in TGFβ signaling. Ubiquitin modifications thus play a key role in TGFβ signal transduction, and in this review we provide an overview of known players, focusing on recent advances.

References

Oct 23, 1997·Nature·T ImamuraK Miyazono
Oct 6, 1998·Annual Review of Biochemistry·A Hershko, A Ciechanover
Dec 10, 1999·Nature Cell Biology·R S Lo, J Massagué
Feb 7, 2001·Proceedings of the National Academy of Sciences of the United States of America·Y ZhangR Derynck
Nov 1, 2002·Molecular Cell·Eva GrönroosJohan Ericsson
May 13, 2003·The Journal of Biological Chemistry·Pierre S W LeeRik Derynck
Jul 15, 2003·Molecular Biology of the Cell·Gyo MurakamiTakeshi Imamura
Dec 6, 2003·The EMBO Journal·Daizo KoinumaKohei Miyazono
Jan 1, 2004·Molecular and Cellular Biology·Linyu LiZhijie Chang
Feb 28, 2004·The Journal of Biological Chemistry·Mei WanXu Cao
Aug 18, 2004·Molecular and Cellular Biology·Min LiangXia Lin
Apr 9, 2005·The Journal of Biological Chemistry·Anita MorénAristidis Moustakas
Apr 16, 2005·The Journal of Biological Chemistry·Maria SimonssonEva Grönroos
Apr 28, 2005·The American Journal of Pathology·Mei WanXu Cao
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elizabeth A WohlfertRobert B Clark
May 25, 2006·Journal of Molecular Endocrinology·T YamaguchiH Sugino
Jun 7, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kenneth W FinnsonAnie Philip
Sep 26, 2006·Trends in Cell Biology·Michael J Clague, Sylvie Urbé

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Citations

Oct 30, 2013·Oncogene·S-M HedeF J Swartling
Sep 25, 2015·Microscopy and Microanalysis : the Official Journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada·Lisa RepsoldAnnie M Joubert
Mar 5, 2014·Targeted Oncology·Laurent-Olivier RoyDavid Fortin
May 8, 2016·The International Journal of Biochemistry & Cell Biology·Sijia LiuPeter Ten Dijke
Dec 10, 2013·Molecular & Cellular Proteomics : MCP·Guoxiong XuMichelle Letarte
Jun 26, 2017·Journal of Molecular Biology·Maria BirkouGeorgios A Spyroulias
Dec 1, 2017·Acta Biochimica Et Biophysica Sinica·Feng XieLong Zhang
May 13, 2015·Molecular and Cellular Biology·Wenjing LiChi-Wing Chow
Oct 20, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Haiwen LiLingqiang Zhang
May 5, 2017·The EMBO Journal·Fangfang ZhouPeter Ten Dijke
Apr 12, 2013·American Journal of Physiology. Renal Physiology·Bryan M Grabias, Konstantinos Konstantopoulos
Aug 3, 2016·Cold Spring Harbor Perspectives in Biology·Carl-Henrik Heldin, Aristidis Moustakas
Jan 11, 2020·Frontiers in Immunology·Karen Slattery, Clair M Gardiner
Oct 18, 2020·International Journal of Molecular Sciences·Wolfgang EberhardtJosef Pfeilschifter
Sep 28, 2014·Cancer Research·Nanyue ChenAnn McNeill Killary
Jan 30, 2021·Circulation Research·Zachary T HiltCraig N Morrell
Jan 10, 2021·International Journal of Molecular Sciences·Abhishek SinhaPeter Ten Dijke
Feb 1, 2014·Molecular & Cellular Proteomics : MCP·Guoxiong XuMichelle Letarte
May 25, 2021·Frontiers in Molecular Biosciences·Ming-Li ZouFeng-Lai Yuan

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Methods Mentioned

BETA
ubiquitination
deubiquitination
ubiquitinate
acetylation

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