Ubiquitylation is one of the most common post-translational modifications, affecting many cellular processes by marking proteins for proteosomal degradation or modulation of protein function. E3 Ubiquitin ligases are a crucial component of the ubiquitylation process, directly catalysing attachment of ubiquitin to substrate proteins. Hence, E3 ligases provide pathway specificity, and have recently become another avenue for the pursuit of targeted cancer therapeutics. UBR5 is an E3 ubiquitin ligase frequently deregulated in cancer, however any biological role in cancer is largely uncharacterised, partly due to a lack of understanding of interacting proteins and pathways.

Analysis of public gene expression datasets, identified significant co-expression of UBR5 and Centrosome and Spindle Pole Associated Protein 1 (CSPP1). CSPP1 is a regulator of cytokenesis and has recently been implicated in breast cancer and ciliopathy. We show that UBR5 directly interacts with, and poly-ubiquitylates, multiple isoforms of CSPP1 and UBR5 depletion by shRNA causes a significant disruption of ciliogenesis. Further, ubiquitomics analysis of breast cancer cells following UBR5 depletion shows that 2 key regulators of ciliogenesis, PCM1 and MIB1 have significantly altered ubiquitylation profiles. Together, these data suggest that UBR5 regulates a network of proteins controlling ciliogenesis.