CEP192 interacts physically and functionally with the K63-deubiquitinase CYLD to promote mitotic spindle assembly

CEP192 is a centrosome protein that plays a critical role in centrosome biogenesis and function in mammals, Drosophila and C. elegans.¹ Dix CI, Raff JW. Drosophila Spd-2 recruits PCM to the sperm centriole, but is dispensable for centriole duplication. Curr Biol 2007; 17:1759 - 64; http://dx.doi.org/10.1016/j.cub.2007.08.065; PMID: 17919907 Crossref], PubMed], Web of Science ®] , Google Scholar]^-6 Gomez-Ferreria MA, Rath U, Buster DW, Chanda SK, Caldwell JS, Rines DR, et al. Human Cep192 is required for mitotic centrosome and spindle assembly. Curr Biol 2007; 17:1960 - 6; http://dx.doi.org/10.1016/j.cub.2007.10.019; PMID: 17980596 Crossref], PubMed], Web of Science ®] , Google Scholar] Moreover, CEP192-depleted cells arrest in mitosis with disorganized microtubules, suggesting that CEP192’s function in spindle assembly goes beyond its role in centrosome activity and pointing to a potentially more direct role in the regulation of the mitotic microtubule landscape.⁷ Gomez-Ferreria MA, Sharp DJ. Cep192 and the generation of the mitotic spindle. Cell Cycle 2008; 7:1507 - 10; http://dx.doi.org/10.4161/cc.7.11.5957; PMID: 18469523 Taylor & Francis Online], Web of Science ®] , Google Scholar] To better understand CEP192 function in mitosis, we used mass spectrometry to identify CEP192-interacting proteins. We previously reported that CEP192 interacts with NEDD1, a protein that associates with the γ-tubulin ring complex (γ-TuRC) and regulates its phosphorylation status during mitosis.⁸ Gomez-Ferreria M, Bashkurov M, Helbig A, Larsen B, Pawson T, Gingras AC, et al. Novel NEDD1 phosphorylation sites regulate γ-tubulin bindingand mitotic spindle assembly. J Cell Sci 2012; http://dx.doi.org/10.1242/jcs.105130; PMID: 22595525 Crossref], PubMed], Web of Science ®] , Google Scholar] Additionally, within the array of proteins that interact with CEP192, we identified the microtubule binding K63-deubiquitinase CYLD. Further analyses show that co-depletion of CYLD alleviates the bipolar spindle assembly defects observed in CEP192-depleted cells. This functional relationship exposes an intriguing role for CYLD in spindle formation and raises the tantalizing possibility that CEP192 promotes robust mitotic spindle assembly by regulating K63-polyubiquitin-mediated signaling through CYLD.