Regulation of the transforming growth factor β pathway by reversible ubiquitylation

The transforming growth factor beta (TGF beta) 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 TGF beta cytokines are intricately regulated by complex biochemical processes. The corruption of these regulatory processes results in aberrant TGF beta 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 TGF beta signals. Many studies have investigated the mechanisms by which various E3 ubiquitin ligases regulate the turnover and activity of TGF beta 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 TGF beta signalling by E3 ubiquitin ligases and deubiquitylases.