The emerging roles of deubiquitylating enzymes (DUBs) in the TGFβ and BMP pathways

The members of the transforming growth factor beta (TGFß) family of cytokines, including bone morphogenetic proteins (BMP), play fundamental roles in development and tissue homeostasis. Hence, aberrant TGFß/BMP signalling is associated with several human diseases such as fibrosis, bone and immune disorders, cancer progression and metastasis. Consequently, targeting TGFß signalling for intervention potentially offers therapeutic opportunities against these diseases. Many investigations have focussed on understanding the molecular mechanisms underpinning the regulation of TGFß signalling. One of the key areas has been to investigate the regulation of the protein components of the TGFß/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 TGFß pathway. However, the research on DUBs regulating the TGFß 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 TGFß signalling