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P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation
The ataxia telangiectasia mutated- and rad3-related kinase (ATR)/Chk1 pathway is a sentinel of cell cycle progression. On the other hand, the Ras/mitogen-activated protein kinase/90-kDa ribosomal S6 kinase (p90 RSK) pathway is a central node in cell signaling downstream of growth factors. These path...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327324/ https://www.ncbi.nlm.nih.gov/pubmed/22357623 http://dx.doi.org/10.1091/mbc.E11-10-0883 |
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author | Li, Ping Goto, Hidemasa Kasahara, Kousuke Matsuyama, Makoto Wang, Zhonghua Yatabe, Yasushi Kiyono, Tohru Inagaki, Masaki |
author_facet | Li, Ping Goto, Hidemasa Kasahara, Kousuke Matsuyama, Makoto Wang, Zhonghua Yatabe, Yasushi Kiyono, Tohru Inagaki, Masaki |
author_sort | Li, Ping |
collection | PubMed |
description | The ataxia telangiectasia mutated- and rad3-related kinase (ATR)/Chk1 pathway is a sentinel of cell cycle progression. On the other hand, the Ras/mitogen-activated protein kinase/90-kDa ribosomal S6 kinase (p90 RSK) pathway is a central node in cell signaling downstream of growth factors. These pathways are closely correlated in cell proliferation, but their interaction is largely unknown. Here we show that Chk1 is phosphorylated predominantly at Ser-280 and translocated from cytoplasm to nucleus in response to serum stimulation. Nonphosphorylated Chk1–Ser-280 mutation attenuates nuclear Chk1 accumulation, whereas the phosphomimic mutation has a reverse effect on the localization. Treatment with p90 RSK inhibitor impairs Chk1 phosphorylation at Ser-280 and accumulation at the nucleus after serum stimulation, whereas these two phenomena are induced by the expression of the constitutively active mutant of p90 RSK in serum-starved cells. In vitro analyses indicate that p90 RSK stoichiometrically phosphorylates Ser-280 on Chk1. Together with Chk1 phosphorylation at Ser-345 by ATR and its autophosphorylation at Ser-296, which are critical for checkpoint signaling, Chk1–Ser-280 phosphorylation is elevated in a p90 RSK–dependent manner after UV irradiation. In addition, Chk1 phosphorylation at Ser-345 and Ser-296 after UV irradiation is also attenuated by the treatment with p90 RSK inhibitor or by Ser-280 mutation to Ala. These results suggest that p90 RSK facilitates nuclear Chk1 accumulation through Chk1–Ser-280 phosphorylation and that this pathway plays an important role in the preparation for monitoring genetic stability during cell proliferation. |
format | Online Article Text |
id | pubmed-3327324 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-33273242012-06-30 P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation Li, Ping Goto, Hidemasa Kasahara, Kousuke Matsuyama, Makoto Wang, Zhonghua Yatabe, Yasushi Kiyono, Tohru Inagaki, Masaki Mol Biol Cell Articles The ataxia telangiectasia mutated- and rad3-related kinase (ATR)/Chk1 pathway is a sentinel of cell cycle progression. On the other hand, the Ras/mitogen-activated protein kinase/90-kDa ribosomal S6 kinase (p90 RSK) pathway is a central node in cell signaling downstream of growth factors. These pathways are closely correlated in cell proliferation, but their interaction is largely unknown. Here we show that Chk1 is phosphorylated predominantly at Ser-280 and translocated from cytoplasm to nucleus in response to serum stimulation. Nonphosphorylated Chk1–Ser-280 mutation attenuates nuclear Chk1 accumulation, whereas the phosphomimic mutation has a reverse effect on the localization. Treatment with p90 RSK inhibitor impairs Chk1 phosphorylation at Ser-280 and accumulation at the nucleus after serum stimulation, whereas these two phenomena are induced by the expression of the constitutively active mutant of p90 RSK in serum-starved cells. In vitro analyses indicate that p90 RSK stoichiometrically phosphorylates Ser-280 on Chk1. Together with Chk1 phosphorylation at Ser-345 by ATR and its autophosphorylation at Ser-296, which are critical for checkpoint signaling, Chk1–Ser-280 phosphorylation is elevated in a p90 RSK–dependent manner after UV irradiation. In addition, Chk1 phosphorylation at Ser-345 and Ser-296 after UV irradiation is also attenuated by the treatment with p90 RSK inhibitor or by Ser-280 mutation to Ala. These results suggest that p90 RSK facilitates nuclear Chk1 accumulation through Chk1–Ser-280 phosphorylation and that this pathway plays an important role in the preparation for monitoring genetic stability during cell proliferation. The American Society for Cell Biology 2012-04-15 /pmc/articles/PMC3327324/ /pubmed/22357623 http://dx.doi.org/10.1091/mbc.E11-10-0883 Text en © 2012 Li 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 Li, Ping Goto, Hidemasa Kasahara, Kousuke Matsuyama, Makoto Wang, Zhonghua Yatabe, Yasushi Kiyono, Tohru Inagaki, Masaki P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation |
title | P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation |
title_full | P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation |
title_fullStr | P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation |
title_full_unstemmed | P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation |
title_short | P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation |
title_sort | p90 rsk arranges chk1 in the nucleus for monitoring of genomic integrity during cell proliferation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327324/ https://www.ncbi.nlm.nih.gov/pubmed/22357623 http://dx.doi.org/10.1091/mbc.E11-10-0883 |
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