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

作者：Chavali Pavithra L; Chandrasekaran Gayathri; Barr Alexis R; Tatrai Peter; Taylor Chris; Papachristou Evaggelia K; Woods C Geoffrey; Chavali Sreenivas; Gergely Fanni^*

来源：Nature Communications, 2016, 7(1): 11005.

DOI：10.1038/ncomms11005

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.

• 出版日期2016-3
• 单位河北医科大学