Regulation of the transforming growth factor b pathway by reversible ubiquitylation

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. Reversible ubiquitylation of pathway components is a key regulatory process that plays a critical role in ensuring a balanced response to TGFb signals. Many studies have investigated the mechanisms by which various E3 ubiquitin ligases regulate the turnover and activity of TGFb 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 TGFb signalling by E3 ubiquitin ligases and deubiquitylases.