@article {Shearer090100, author = {Robert F. Shearer and Kari-Anne Myrum Frikstad and Jessie McKenna and Rachael A. McCloy and Niantao Deng and Andrew Burgess and Trond Stokke and Sebastian Patzke and Darren N. Saunders}, title = {The E3 ubiquitin ligase UBR5 regulates centriolar satellite stability and primary cilia formation via ubiquitylation of CSPP-L}, elocation-id = {090100}, year = {2016}, doi = {10.1101/090100}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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 modulator of ciliogenesis in a functional genomics screen. UBR5 is an E3 Ubiquitin ligase that is frequently deregulated in tumours, but its biological role in cancer is largely uncharacterised, 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. Hence, we have established a key role for UBR5 in ciliogenesis that may have important implications in understanding cancer pathophysiology.}, URL = {https://www.biorxiv.org/content/early/2016/12/22/090100}, eprint = {https://www.biorxiv.org/content/early/2016/12/22/090100.full.pdf}, journal = {bioRxiv} }