Abstract
The transforming growth factor β (TGFβ) signalling pathway plays a central role during embryonic development and in adult tissue homeostasis. It regulates gene transcription through a signalling cascade from cell surface receptors to intracellular SMAD transcription factors and their nuclear cofactors. The extent, duration and potency of signalling in response to TGFβ cytokines are intricately regulated by complex biochemical processes. The corruption of these regulatory processes results in aberrant TGFβ signalling and leads to numerous human diseases, including cancer. Reversible ubiquitylation of pathway components is a key regulatory process that plays a critical role in ensuring a balanced response to TGFβ signals. Many studies have investigated the mechanisms by which various E3 ubiquitin ligases regulate the turnover and activity of TGFβ pathway components by ubiquitylation. Moreover, recent studies have shed new light into their regulation by deubiquitylating enzymes. In this report, we provide an overview of current understanding of the regulation of TGFβ signalling by E3 ubiquitin ligases and deubiquitylases.
Highlights
The transforming growth factor b (TGFb) family of cytokines control a plethora of cellular processes, including proliferation, differentiation, extra-cellular matrix production, motility and survival [1,2]
While we focus on the role of reversible ubiquitylation in regulating the core components of the TGFb pathway in this review, they can be further regulated by multiple post-translational modifications, which impact the outcome of TGFb signalling
We focus on our understanding of how reversible ubiquitylation impacts three groups of key TGFb pathway mediators: the TGFb receptors, the SMAD transcription factors and nuclear SMAD cofactors
Summary
The transforming growth factor b (TGFb) signalling pathway plays a central role during embryonic development and in adult tissue homeostasis. It regulates gene transcription through a signalling cascade from cell surface receptors to intracellular SMAD transcription factors and their nuclear cofactors. The extent, duration and potency of signalling in response to TGFb cytokines are intricately regulated by complex biochemical processes. The corruption of these regulatory processes results in aberrant TGFb signalling and leads to numerous human diseases, including cancer. Many studies have investigated the mechanisms by which various E3 ubiquitin ligases regulate the turnover and activity of TGFb pathway components by ubiquitylation. We provide an overview of current understanding of the regulation of TGFb signalling by E3 ubiquitin ligases and deubiquitylases
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call