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

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. Althou...

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Autores principales: Chavali, Pavithra L., Chandrasekaran, Gayathri, Barr, Alexis R., Tátrai, Péter, Taylor, Chris, Papachristou, Evaggelia K., Woods, C. Geoffrey, Chavali, Sreenivas, Gergely, Fanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802056/
https://www.ncbi.nlm.nih.gov/pubmed/26987684
http://dx.doi.org/10.1038/ncomms11005
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author Chavali, Pavithra L.
Chandrasekaran, Gayathri
Barr, Alexis R.
Tátrai, Péter
Taylor, Chris
Papachristou, Evaggelia K.
Woods, C. Geoffrey
Chavali, Sreenivas
Gergely, Fanni
author_facet Chavali, Pavithra L.
Chandrasekaran, Gayathri
Barr, Alexis R.
Tátrai, Péter
Taylor, Chris
Papachristou, Evaggelia K.
Woods, C. Geoffrey
Chavali, Sreenivas
Gergely, Fanni
author_sort Chavali, Pavithra L.
collection PubMed
description 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.
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spelling pubmed-48020562016-03-25 A CEP215–HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer Chavali, Pavithra L. Chandrasekaran, Gayathri Barr, Alexis R. Tátrai, Péter Taylor, Chris Papachristou, Evaggelia K. Woods, C. Geoffrey Chavali, Sreenivas Gergely, Fanni Nat Commun Article 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. Nature Publishing Group 2016-03-18 /pmc/articles/PMC4802056/ /pubmed/26987684 http://dx.doi.org/10.1038/ncomms11005 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Chavali, Pavithra L.
Chandrasekaran, Gayathri
Barr, Alexis R.
Tátrai, Péter
Taylor, Chris
Papachristou, Evaggelia K.
Woods, C. Geoffrey
Chavali, Sreenivas
Gergely, Fanni
A CEP215–HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer
title A CEP215–HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer
title_full A CEP215–HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer
title_fullStr A CEP215–HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer
title_full_unstemmed A CEP215–HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer
title_short A CEP215–HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer
title_sort cep215–hset complex links centrosomes with spindle poles and drives centrosome clustering in cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802056/
https://www.ncbi.nlm.nih.gov/pubmed/26987684
http://dx.doi.org/10.1038/ncomms11005
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