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Protein kinase Cδ regulates vaccinia-related kinase 1 in DNA damage–induced apoptosis

Vaccinia-related kinase 1 (VRK1) is a novel serine/threonine kinase that plays an important role in cell proliferation. However, little is known about the upstream regulators of VRK1 activity. Here we provide evidence for a role of protein kinase Cδ (PKCδ) in the regulation of murine VRK1. We show t...

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Autores principales: Park, Choon-Ho, Choi, Bo-Hwa, Jeong, Min-Woo, Kim, Sangjune, Kim, Wanil, Song, Yun Seon, Kim, Kyong-Tai
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078082/
https://www.ncbi.nlm.nih.gov/pubmed/21346188
http://dx.doi.org/10.1091/mbc.E10-08-0717
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author Park, Choon-Ho
Choi, Bo-Hwa
Jeong, Min-Woo
Kim, Sangjune
Kim, Wanil
Song, Yun Seon
Kim, Kyong-Tai
author_facet Park, Choon-Ho
Choi, Bo-Hwa
Jeong, Min-Woo
Kim, Sangjune
Kim, Wanil
Song, Yun Seon
Kim, Kyong-Tai
author_sort Park, Choon-Ho
collection PubMed
description Vaccinia-related kinase 1 (VRK1) is a novel serine/threonine kinase that plays an important role in cell proliferation. However, little is known about the upstream regulators of VRK1 activity. Here we provide evidence for a role of protein kinase Cδ (PKCδ) in the regulation of murine VRK1. We show that PKCδ interacts with VRK1, phosphorylates the Ser-355 residue in the putative regulatory region, and negatively regulates its kinase activity in vitro. Intriguingly, PKCδ-induced cell death was facilitated by phosphorylation of VRK1 when cells were exposed to a DNA-damaging agent. In addition, p53 played a critical role in the regulation of DNA damage–induced cell death accompanied by PKCδ-mediated modulation of VRK1. In p53-deficient cells, PKCδ-mediated phosphorylation of VRK1 had no effect on cell viability. However, cells overexpressing p53 exhibited significant reduction of cell viability when cotransfected with both VRK1 and PKCδ. Taken together, these results indicate that PKCδ regulates phosphorylation and down-regulation of VRK1, thereby contributing to cell cycle arrest and apoptotic cell death in a p53-dependent manner.
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spelling pubmed-30780822011-06-30 Protein kinase Cδ regulates vaccinia-related kinase 1 in DNA damage–induced apoptosis Park, Choon-Ho Choi, Bo-Hwa Jeong, Min-Woo Kim, Sangjune Kim, Wanil Song, Yun Seon Kim, Kyong-Tai Mol Biol Cell Articles Vaccinia-related kinase 1 (VRK1) is a novel serine/threonine kinase that plays an important role in cell proliferation. However, little is known about the upstream regulators of VRK1 activity. Here we provide evidence for a role of protein kinase Cδ (PKCδ) in the regulation of murine VRK1. We show that PKCδ interacts with VRK1, phosphorylates the Ser-355 residue in the putative regulatory region, and negatively regulates its kinase activity in vitro. Intriguingly, PKCδ-induced cell death was facilitated by phosphorylation of VRK1 when cells were exposed to a DNA-damaging agent. In addition, p53 played a critical role in the regulation of DNA damage–induced cell death accompanied by PKCδ-mediated modulation of VRK1. In p53-deficient cells, PKCδ-mediated phosphorylation of VRK1 had no effect on cell viability. However, cells overexpressing p53 exhibited significant reduction of cell viability when cotransfected with both VRK1 and PKCδ. Taken together, these results indicate that PKCδ regulates phosphorylation and down-regulation of VRK1, thereby contributing to cell cycle arrest and apoptotic cell death in a p53-dependent manner. The American Society for Cell Biology 2011-04-15 /pmc/articles/PMC3078082/ /pubmed/21346188 http://dx.doi.org/10.1091/mbc.E10-08-0717 Text en © 2011 Park et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,“ “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Park, Choon-Ho
Choi, Bo-Hwa
Jeong, Min-Woo
Kim, Sangjune
Kim, Wanil
Song, Yun Seon
Kim, Kyong-Tai
Protein kinase Cδ regulates vaccinia-related kinase 1 in DNA damage–induced apoptosis
title Protein kinase Cδ regulates vaccinia-related kinase 1 in DNA damage–induced apoptosis
title_full Protein kinase Cδ regulates vaccinia-related kinase 1 in DNA damage–induced apoptosis
title_fullStr Protein kinase Cδ regulates vaccinia-related kinase 1 in DNA damage–induced apoptosis
title_full_unstemmed Protein kinase Cδ regulates vaccinia-related kinase 1 in DNA damage–induced apoptosis
title_short Protein kinase Cδ regulates vaccinia-related kinase 1 in DNA damage–induced apoptosis
title_sort protein kinase cδ regulates vaccinia-related kinase 1 in dna damage–induced apoptosis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3078082/
https://www.ncbi.nlm.nih.gov/pubmed/21346188
http://dx.doi.org/10.1091/mbc.E10-08-0717
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