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. 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. 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. 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.
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Maria Ana
MA
Gomez-Ferreria
Mikhail
M
Bashkurov
Michael
M
Mullin
Anne-Claude
AC
Gingras
Laurence
L
Pelletier
D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D000074749:Deubiquitinating Enzyme CYLD; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008239:Lysine / Q000378:metabolism*; D013058:Mass Spectrometry; D011485:Protein Binding; D008941:Spindle Apparatus / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
C526596:Cep192 protein, human; D002868:Chromosomal Proteins, Non-Histone; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD; D008239:Lysine