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CDK-Mediated Regulation of Cell Functions via c-Jun Phosphorylation and AP-1 Activation
Cyclin-dependent kinases (CDKs) and their targets have been primarily associated with regulation of cell-cycle progression. Here we identify c-Jun, a transcription factor involved in the regulation of a broad spectrum of cellular functions, as a newly recognized CDK substrate. Using immune cells fro...
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084876/ https://www.ncbi.nlm.nih.gov/pubmed/21559334 http://dx.doi.org/10.1371/journal.pone.0019468 |
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author | Vanden Bush, Tony J. Bishop, Gail A. |
author_facet | Vanden Bush, Tony J. Bishop, Gail A. |
author_sort | Vanden Bush, Tony J. |
collection | PubMed |
description | Cyclin-dependent kinases (CDKs) and their targets have been primarily associated with regulation of cell-cycle progression. Here we identify c-Jun, a transcription factor involved in the regulation of a broad spectrum of cellular functions, as a newly recognized CDK substrate. Using immune cells from mouse and human, and several complementary in vitro and in vivo approaches including dominant negative protein expression, pharmacologic inhibitors, kinase assays and CDK4 deficient cells, we demonstrate the ability of CDK4 to phosphorylate c-Jun. Additionally, the activity of AP-1, a ubiquitous transcription factor containing phosphorylated c-Jun as a subunit, was inhibited by abrogating CDK4. Surprisingly, the regulation of c-Jun phosphorylation by CDK4 occurred in non-dividing cells, indicating that this pathway is utilized for cell functions that are independent of proliferation. Our studies identify a new substrate for CDK4 and suggest a mechanism by which CDKs can regulate multiple cellular activation functions, not all of which are directly associated with cell cycle progression. These findings point to additional roles of CDKs in cell signaling and reveal potential implications for therapeutic manipulations of this kinase pathway. |
format | Text |
id | pubmed-3084876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30848762011-05-10 CDK-Mediated Regulation of Cell Functions via c-Jun Phosphorylation and AP-1 Activation Vanden Bush, Tony J. Bishop, Gail A. PLoS One Research Article Cyclin-dependent kinases (CDKs) and their targets have been primarily associated with regulation of cell-cycle progression. Here we identify c-Jun, a transcription factor involved in the regulation of a broad spectrum of cellular functions, as a newly recognized CDK substrate. Using immune cells from mouse and human, and several complementary in vitro and in vivo approaches including dominant negative protein expression, pharmacologic inhibitors, kinase assays and CDK4 deficient cells, we demonstrate the ability of CDK4 to phosphorylate c-Jun. Additionally, the activity of AP-1, a ubiquitous transcription factor containing phosphorylated c-Jun as a subunit, was inhibited by abrogating CDK4. Surprisingly, the regulation of c-Jun phosphorylation by CDK4 occurred in non-dividing cells, indicating that this pathway is utilized for cell functions that are independent of proliferation. Our studies identify a new substrate for CDK4 and suggest a mechanism by which CDKs can regulate multiple cellular activation functions, not all of which are directly associated with cell cycle progression. These findings point to additional roles of CDKs in cell signaling and reveal potential implications for therapeutic manipulations of this kinase pathway. Public Library of Science 2011-04-29 /pmc/articles/PMC3084876/ /pubmed/21559334 http://dx.doi.org/10.1371/journal.pone.0019468 Text en Vanden Bush, Bishop. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Vanden Bush, Tony J. Bishop, Gail A. CDK-Mediated Regulation of Cell Functions via c-Jun Phosphorylation and AP-1 Activation |
title | CDK-Mediated Regulation of Cell Functions via c-Jun Phosphorylation
and AP-1 Activation |
title_full | CDK-Mediated Regulation of Cell Functions via c-Jun Phosphorylation
and AP-1 Activation |
title_fullStr | CDK-Mediated Regulation of Cell Functions via c-Jun Phosphorylation
and AP-1 Activation |
title_full_unstemmed | CDK-Mediated Regulation of Cell Functions via c-Jun Phosphorylation
and AP-1 Activation |
title_short | CDK-Mediated Regulation of Cell Functions via c-Jun Phosphorylation
and AP-1 Activation |
title_sort | cdk-mediated regulation of cell functions via c-jun phosphorylation
and ap-1 activation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084876/ https://www.ncbi.nlm.nih.gov/pubmed/21559334 http://dx.doi.org/10.1371/journal.pone.0019468 |
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