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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...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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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. |
format | Text |
id | pubmed-2064305 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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