Regulation of the transforming growth factor β pathway by reversible ubiquitylation.
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.
Medical Research Council-Protein Phosphorylation Unit, Sir James Black Centre, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
Mazin A
MA
Al-Salihi
Lina
L
Herhaus
Gopal P
GP
Sapkota
D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000502:physiology; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D057056:Cysteine Proteases / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006657:Histones / Q000502:physiology; D006801:Humans; D045726:Metalloproteases / Q000502:physiology; D008954:Models, Biological; D009687:Nuclear Proteins / Q000502:physiology; D011499:Protein Processing, Post-Translational; D018125:Receptors, Transforming Growth Factor beta / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051785:Smad Proteins / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D057149:Ubiquitinated Proteins / Q000378:metabolism; D054875:Ubiquitination
D019485:Bone Morphogenetic Proteins; D006657:Histones; D009687:Nuclear Proteins; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D025801:Ubiquitin; D057149:Ubiquitinated Proteins; D052004:Bone Morphogenetic Protein Receptors; D057056:Cysteine Proteases; D045726:Metalloproteases