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The E3 ubiquitin ligase UBR5 regulates centriolar satellite stability and primary cilia


Primary cilia are crucial for signal transduction in a variety of pathways, including hedgehog and Wnt. Disruption of primary cilia formation (ciliogenesis) is linked to numerous developmental disorders (known as ciliopathies) and diseases, including cancer. The ubiquitin-proteasome system (UPS) component UBR5 was previously identified as a putative positive regulator of ciliogenesis in a functional genomics screen. UBR5 is an E3 ubiquitin ligase that is frequently deregulated in tumors, but its biological role in cancer is largely uncharacterized, partly due to a lack of understanding of interacting proteins and pathways. We validated the effect of UBR5 depletion on primary cilia formation using a robust model of ciliogenesis, and identified CSPP1, a centrosomal and ciliary protein required for cilia formation, as a UBR5-interacting protein. We show that UBR5 ubiquitylates CSPP1, and that UBR5 is required for cytoplasmic organization of CSPP1-comprising centriolar satellites in centrosomal periphery, suggesting that UBR5-mediated ubiquitylation of CSPP1 or associated centriolar satellite constituents is one underlying requirement for cilia expression. Hence, we have established a key role for UBR5 in ciliogenesis that may have important implications in understanding cancer pathophysiology.

Type Journal
ISBN 1939-4586 (Electronic) 1059-1524 (Linking)
Authors Shearer, R. F.; Frikstad, K. M.; McKenna, J.; McCloy, R. A.; Deng, N.; Burgess, A.; Stokke, T.; Patzke, S.; Saunders, D. N.
Responsible Garvan Author Rachael Zekanovic
Published Date 2018-07-01
Published Volume 29
Published Issue 13
Published Pages 1542-1554
Status Published in-print
DOI 10.1091/mbc.E17-04-0248
URL link to publisher's version
OpenAccess link to author's accepted manuscript version