Pharmaceutical Perspectives of HECT-TYPE Ubiquitin Ligase Smurf1

Yu      Cao; Lingqiang      Zhang

doi:10.2174/1381612811319180007

Abstract

Smad ubiquitylation regulatory factor-1 (Smurf1) is a HECT-type ubiquitin ligase. The role of Smurf1 in cell development and migration, viral autophagy and immune responses has been the subject of intensive study in recent years. Smurf1 regulates multiple biological networks, including TGF-β and BMP signaling pathways, the non-canonical pathway and the Toll-like receptor pathway, and is linked to certain diseases and disorders, such as bone formation and embryonic development disorders. Increasing evidence suggests that Smurf1 could be a good candidate for further translational studies and a potential target for novel drug design. In this review, we summarize the physiological functions of Smurf1 and its associated disorders; and discuss the current state of drug discovery in the context of the ubiquitin-proteasomal system, and feasible pharmaceutical strategies toward Smurf1 and its regulators, as well as RNA interference and structure-based chemical drug selection.

Keywords: Ubiquitylation, Ubiquitin ligase, HECT domain, Nedd4 family, Smurf1.

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