title: The emerging roles of deubiquitylating enzymes (DUBs) in the TGFβ and BMP pathways.
abstract: The members of the transforming growth factor beta (TGFβ) family of cytokines, including bone morphogenetic proteins (BMP), play fundamental roles in development and tissue homeostasis. Hence, aberrant TGFβ/BMP signalling is associated with several human diseases such as fibrosis, bone and immune disorders, cancer progression and metastasis. Consequently, targeting TGFβ signalling for intervention potentially offers therapeutic opportunities against these diseases. Many investigations have focussed on understanding the molecular mechanisms underpinning the regulation of TGFβ signalling. One of the key areas has been to investigate the regulation of the protein components of the TGFβ/BMP signal transduction pathways by ubiquitylation and deubiquitylation. In the last 15years, extensive research has led to the discovery and characterisation of several E3 ubiquitin ligases that influence the TGFβ pathway. However, the research on DUBs regulating the TGFβ pathway has received prominence only recently and is still an emerging field. This review will provide a concise summary of our current understanding of how DUBs regulate TGFβ signalling.
authors.affiliation: MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, United Kingdom.
authors.forename: Lina
authors.initials: L
authors.lastname: Herhaus
authors.affiliation: MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH Scotland, United Kingdom. Electronic address: g.sapkota@dundee.ac.uk.
authors.forename: Gopal P
authors.initials: GP
authors.lastname: Sapkota
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction; D051896:Smad Proteins, Receptor-Regulated / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D019485:Bone Morphogenetic Proteins; D051896:Smad Proteins, Receptor-Regulated; D051901:Smad4 Protein; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase
keywords: BMP; DUB; Deubiquitylation; SMAD; TGF-beta; Ubiquitin