Journal
JOURNAL OF BIOCHEMISTRY
Volume 154, Issue 6, Pages 481-489Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jb/mvt097
Keywords
deubiquitination; E3 ubiquitin ligases; TGF-beta ubiquitination; Ubiquitin-proteasome system
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
- Grants-in-Aid for Scientific Research [22113004] Funding Source: KAKEN
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Members of the transforming growth factor-beta (TGF-beta) family, including TGF-beta s, activin and bone morphogenetic proteins (BMPs), are multifunctional proteins that regulate a wide variety of cellular responses, such as proliferation, differentiation, migration and apoptosis. TGF-beta family signalling is mainly mediated by membranous serine/threonine kinase receptors and intracellular Smad proteins. This signalling is tightly regulated by various post-translational modifications including ubiquitination. Several E3 ubiquitin ligases play a crucial role in the recognition and ubiquitin-dependent degradation of TGF-beta family receptors, Smad proteins and their interacted proteins to regulate positively and negatively TGF-beta family signalling. In contrast, non-degradative ubiquitin modifications also regulate TGF-beta family signalling. Recently, in addition to protein ubiquitination, deubiquitination by deubiquitinating enzymes has been reported to control TGF-beta family signalling pathways. Interestingly, more recent studies suggest that TGF-beta signalling is not only regulated via ubiquitination and/or deubiquitination, but also it relies on ubiquitination for its effect on other pathways. Thus, ubiquitin modifications play key roles in TGF-beta family signal transduction and cross-talk between TGF-beta family signalling and other signalling pathways. Here, we review the current understandings of the positive and negative regulatory mechanisms by ubiquitin modifications that control TGF-beta family signalling.
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