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A CEP215-HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer.

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Chavali, Pavithra L 
Chandrasekaran, Gayathri 
Barr, Alexis R 
Tátrai, Péter 
Taylor, Chris 


Numerical centrosome aberrations underlie certain developmental abnormalities and may promote cancer. A cell maintains normal centrosome numbers by coupling centrosome duplication with segregation, which is achieved through sustained association of each centrosome with a mitotic spindle pole. Although the microcephaly- and primordial dwarfism-linked centrosomal protein CEP215 has been implicated in this process, the molecular mechanism responsible remains unclear. Here, using proteomic profiling, we identify the minus end-directed microtubule motor protein HSET as a direct binding partner of CEP215. Targeted deletion of the HSET-binding domain of CEP215 in vertebrate cells causes centrosome detachment and results in HSET depletion at centrosomes, a phenotype also observed in CEP215-deficient patient-derived cells. Moreover, in cancer cells with centrosome amplification, the CEP215-HSET complex promotes the clustering of extra centrosomes into pseudo-bipolar spindles, thereby ensuring viable cell division. Therefore, stabilization of the centrosome-spindle pole interface by the CEP215-HSET complex could promote survival of cancer cells containing supernumerary centrosomes.



Animals, Cell Cycle Proteins, Cell Line, Centrosome, Chickens, Cluster Analysis, Humans, Intracellular Signaling Peptides and Proteins, Kinesins, Mice, Mutation, Neoplasms, Nerve Tissue Proteins, Protein Binding, Protein Interaction Maps, Protein Structure, Tertiary, Spindle Poles

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Nat Commun

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Springer Science and Business Media LLC
S.C. is supported by UK Medical Research Council (MC_U105185859). This work was made possible by funding from Cancer Research UK (C14303/A17197). We acknowledge the support of the University of Cambridge and Hutchison Whampoa Ltd.