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


ABSTRACT: 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 ?-tubulin ring complex (?-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.

SUBMITTER: Gomez-Ferreria MA 

PROVIDER: S-EPMC3478306 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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

Gomez-Ferreria Maria Ana MA   Bashkurov Mikhail M   Mullin Michael M   Gingras Anne-Claude AC   Pelletier Laurence L  

Cell cycle (Georgetown, Tex.) 20120816 19


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 iden  ...[more]

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