Great news, we have recently published a co-author paper in collaboration with Darren Saunders Lab entitled “The E3 ubiquitin ligase UBR5 regulates centriolar satellite stability and primary cilia”. The work was pioneered by a very talented student (now Doctor), Robert Shearer.
You can access the full article here [Link]
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 ubiqui- tin–proteasome system (UPS) component UBR5 was previously identified as a putative posi- tive 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 uncharac- terized, 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 forma- tion, 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 centro- somal periphery, suggesting that UBR5-mediated ubiquitylation of CSPP1 or associated cen- triolar 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.
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