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.
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October 2016
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Cover Image
Cover Image
Alternative splicing of intrinsically disordered segments can rewire protein interaction networks. In this issue, the Biochemical Society’s Colworth Medal winner, M. Madan Babu explores the contribution of intrinsically disordered regions to protein function, cellular complexity and human disease; see pages 1185–1200. [Credit: Guilhem Chalancon, MRC Laboratory of Molecular Biology, Cambridge, UK.]
Review Article|
October 19 2016
Regulation of primary cilia formation by the ubiquitin–proteasome system
Robert F. Shearer;
Robert F. Shearer
1Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, Australia
2St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia
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Darren N. Saunders
Darren N. Saunders
1Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, Australia
3School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia
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Publisher: Portland Press Ltd
Received:
June 15 2016
Revision Received:
July 18 2016
Accepted:
July 19 2016
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2016
Biochem Soc Trans (2016) 44 (5): 1265–1271.
Article history
Received:
June 15 2016
Revision Received:
July 18 2016
Accepted:
July 19 2016
Citation
Robert F. Shearer, Darren N. Saunders; Regulation of primary cilia formation by the ubiquitin–proteasome system. Biochem Soc Trans 15 October 2016; 44 (5): 1265–1271. doi: https://doi.org/10.1042/BST20160174
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