title: Regulation of primary cilia formation by the ubiquitin-proteasome system.
abstract: Primary cilia form at the surface of most vertebrate cell types, where they are essential signalling antennae for signal transduction pathways important for development and cancer, including Hedgehog. The importance of primary cilia in development is clearly demonstrated by numerous disorders (known as ciliopathies) associated with disrupted cilia formation (ciliogenesis). Recent advances describing functional regulators of the primary cilium highlight an emerging role for the ubiquitin-proteasome system (UPS) as a key regulator of ciliogenesis. Although there are well-documented examples of E3 ubiquitin ligases and deubiquitases in the regulation of cilia proteins, many putative components remain unvalidated. This review explores current understanding of how the UPS influences primary cilia formation, and also how recent screen data have identified more putative regulators of the UPS. Emerging research has identified many promising leads in the search for regulators of this important organelle and may identify potential novel therapeutic targets for intervention in cancer and other disease contexts.
authors.affiliation: Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, Australia.|St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Shearer
authors.affiliation: Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, Australia.|School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Darren N
authors.initials: DN
authors.lastname: Saunders
mesh_terms: D000818:Animals; D002923:Cilia / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D020543:Proteome / Q000378:metabolism; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D020543:Proteome; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
keywords: MIB1; cancer; centrosomes; cilia; proteasome; ubiquitin