PT  - JOURNAL ARTICLE
AU  - Robert F. Shearer
AU  - Kari-Anne Myrum Frikstad
AU  - Jessie McKenna
AU  - Rachael A. McCloy
AU  - Niantao Deng
AU  - Andrew Burgess
AU  - Trond Stokke
AU  - Sebastian Patzke
AU  - Darren N. Saunders
TI  - The E3 ubiquitin ligase UBR5 regulates centriolar satellite stability and primary cilia formation via ubiquitylation of CSPP-L
AID  - 10.1101/090100
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 090100
4099  - http://biorxiv.org/content/early/2016/12/22/090100.short
4100  - http://biorxiv.org/content/early/2016/12/22/090100.full
AB  - 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.