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Inhibition of centrosome protein assembly leads to p53-dependent exit from the cell cycle

Previous evidence has indicated that an intact centrosome is essential for cell cycle progress and that elimination of the centrosome or depletion of individual centrosome proteins prevents the entry into S phase. To investigate the molecular mechanisms of centrosome-dependent cell cycle progress, w...

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Detalles Bibliográficos
Autores principales: Srsen, Vlastimil, Gnadt, Nicole, Dammermann, Alexander, Merdes, Andreas
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064305/
https://www.ncbi.nlm.nih.gov/pubmed/16943179
http://dx.doi.org/10.1083/jcb.200606051
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author Srsen, Vlastimil
Gnadt, Nicole
Dammermann, Alexander
Merdes, Andreas
author_facet Srsen, Vlastimil
Gnadt, Nicole
Dammermann, Alexander
Merdes, Andreas
author_sort Srsen, Vlastimil
collection PubMed
description Previous evidence has indicated that an intact centrosome is essential for cell cycle progress and that elimination of the centrosome or depletion of individual centrosome proteins prevents the entry into S phase. To investigate the molecular mechanisms of centrosome-dependent cell cycle progress, we performed RNA silencing experiments of two centrosome-associated proteins, pericentriolar material 1 (PCM-1) and pericentrin, in primary human fibroblasts. We found that cells depleted of PCM-1 or pericentrin show lower levels of markers for S phase and cell proliferation, including cyclin A, Ki-67, proliferating cell nuclear antigen, minichromosome maintenance deficient 3, and phosphorylated retinoblastoma protein. Also, the percentage of cells undergoing DNA replication was reduced by >50%. At the same time, levels of p53 and p21 increased in these cells, and cells were predisposed to undergo senescence. Conversely, depletion of centrosome proteins in cells lacking p53 did not cause any cell cycle arrest. Inhibition of p38 mitogen-activated protein kinase rescued cell cycle activity after centrosome protein depletion, indicating that p53 is activated by the p38 stress pathway.
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spelling pubmed-20643052007-11-29 Inhibition of centrosome protein assembly leads to p53-dependent exit from the cell cycle Srsen, Vlastimil Gnadt, Nicole Dammermann, Alexander Merdes, Andreas J Cell Biol Research Articles Previous evidence has indicated that an intact centrosome is essential for cell cycle progress and that elimination of the centrosome or depletion of individual centrosome proteins prevents the entry into S phase. To investigate the molecular mechanisms of centrosome-dependent cell cycle progress, we performed RNA silencing experiments of two centrosome-associated proteins, pericentriolar material 1 (PCM-1) and pericentrin, in primary human fibroblasts. We found that cells depleted of PCM-1 or pericentrin show lower levels of markers for S phase and cell proliferation, including cyclin A, Ki-67, proliferating cell nuclear antigen, minichromosome maintenance deficient 3, and phosphorylated retinoblastoma protein. Also, the percentage of cells undergoing DNA replication was reduced by >50%. At the same time, levels of p53 and p21 increased in these cells, and cells were predisposed to undergo senescence. Conversely, depletion of centrosome proteins in cells lacking p53 did not cause any cell cycle arrest. Inhibition of p38 mitogen-activated protein kinase rescued cell cycle activity after centrosome protein depletion, indicating that p53 is activated by the p38 stress pathway. The Rockefeller University Press 2006-08-28 /pmc/articles/PMC2064305/ /pubmed/16943179 http://dx.doi.org/10.1083/jcb.200606051 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Srsen, Vlastimil
Gnadt, Nicole
Dammermann, Alexander
Merdes, Andreas
Inhibition of centrosome protein assembly leads to p53-dependent exit from the cell cycle
title Inhibition of centrosome protein assembly leads to p53-dependent exit from the cell cycle
title_full Inhibition of centrosome protein assembly leads to p53-dependent exit from the cell cycle
title_fullStr Inhibition of centrosome protein assembly leads to p53-dependent exit from the cell cycle
title_full_unstemmed Inhibition of centrosome protein assembly leads to p53-dependent exit from the cell cycle
title_short Inhibition of centrosome protein assembly leads to p53-dependent exit from the cell cycle
title_sort inhibition of centrosome protein assembly leads to p53-dependent exit from the cell cycle
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064305/
https://www.ncbi.nlm.nih.gov/pubmed/16943179
http://dx.doi.org/10.1083/jcb.200606051
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