Regulation of Genotoxic Stress Response by Homeodomain-interacting Protein Kinase 2 through Phosphorylation of Cyclic AMP Response Element-binding Protein at Serine 271

CREB (cyclic AMP response element-binding protein) is a stimulus-induced transcription factor that plays pivotal roles in cell survival and proliferation. The transactivation function of CREB is primarily regulated through Ser-133 phosphorylation by cAMP-dependent protein kinase A (PKA) and related...

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Autores principales: Sakamoto, Kensuke, Huang, Bo-Wen, Iwasaki, Kenta, Hailemariam, Kiros, Ninomiya-Tsuji, Jun, Tsuji, Yoshiaki
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921112/
https://www.ncbi.nlm.nih.gov/pubmed/20573984
http://dx.doi.org/10.1091/mbc.E10-01-0015
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author Sakamoto, Kensuke
Huang, Bo-Wen
Iwasaki, Kenta
Hailemariam, Kiros
Ninomiya-Tsuji, Jun
Tsuji, Yoshiaki
author_facet Sakamoto, Kensuke
Huang, Bo-Wen
Iwasaki, Kenta
Hailemariam, Kiros
Ninomiya-Tsuji, Jun
Tsuji, Yoshiaki
author_sort Sakamoto, Kensuke
collection PubMed
description CREB (cyclic AMP response element-binding protein) is a stimulus-induced transcription factor that plays pivotal roles in cell survival and proliferation. The transactivation function of CREB is primarily regulated through Ser-133 phosphorylation by cAMP-dependent protein kinase A (PKA) and related kinases. Here we found that homeodomain-interacting protein kinase 2 (HIPK2), a DNA-damage responsive nuclear kinase, is a new CREB kinase for phosphorylation at Ser-271 but not Ser-133, and activates CREB transactivation function including brain-derived neurotrophic factor (BDNF) mRNA expression. Ser-271 to Glu-271 substitution potentiated the CREB transactivation function. ChIP assays in SH-SY5Y neuroblastoma cells demonstrated that CREB Ser-271 phosphorylation by HIPK2 increased recruitment of a transcriptional coactivator CBP (CREB binding protein) without modulation of CREB binding to the BDNF CRE sequence. HIPK2−/− MEF cells were more susceptible to apoptosis induced by etoposide, a DNA-damaging agent, than HIPK2+/+ cells. Etoposide activated CRE-dependent transcription in HIPK2+/+ MEF cells but not in HIPK2−/− cells. HIPK2 knockdown in SH-SY5Y cells decreased etoposide-induced BDNF mRNA expression. These results demonstrate that HIPK2 is a new CREB kinase that regulates CREB-dependent transcription in genotoxic stress.
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spelling pubmed-29211122010-10-30 Regulation of Genotoxic Stress Response by Homeodomain-interacting Protein Kinase 2 through Phosphorylation of Cyclic AMP Response Element-binding Protein at Serine 271 Sakamoto, Kensuke Huang, Bo-Wen Iwasaki, Kenta Hailemariam, Kiros Ninomiya-Tsuji, Jun Tsuji, Yoshiaki Mol Biol Cell Articles CREB (cyclic AMP response element-binding protein) is a stimulus-induced transcription factor that plays pivotal roles in cell survival and proliferation. The transactivation function of CREB is primarily regulated through Ser-133 phosphorylation by cAMP-dependent protein kinase A (PKA) and related kinases. Here we found that homeodomain-interacting protein kinase 2 (HIPK2), a DNA-damage responsive nuclear kinase, is a new CREB kinase for phosphorylation at Ser-271 but not Ser-133, and activates CREB transactivation function including brain-derived neurotrophic factor (BDNF) mRNA expression. Ser-271 to Glu-271 substitution potentiated the CREB transactivation function. ChIP assays in SH-SY5Y neuroblastoma cells demonstrated that CREB Ser-271 phosphorylation by HIPK2 increased recruitment of a transcriptional coactivator CBP (CREB binding protein) without modulation of CREB binding to the BDNF CRE sequence. HIPK2−/− MEF cells were more susceptible to apoptosis induced by etoposide, a DNA-damaging agent, than HIPK2+/+ cells. Etoposide activated CRE-dependent transcription in HIPK2+/+ MEF cells but not in HIPK2−/− cells. HIPK2 knockdown in SH-SY5Y cells decreased etoposide-induced BDNF mRNA expression. These results demonstrate that HIPK2 is a new CREB kinase that regulates CREB-dependent transcription in genotoxic stress. The American Society for Cell Biology 2010-08-15 /pmc/articles/PMC2921112/ /pubmed/20573984 http://dx.doi.org/10.1091/mbc.E10-01-0015 Text en © 2010 by The American Society for Cell Biology
spellingShingle Articles
Sakamoto, Kensuke
Huang, Bo-Wen
Iwasaki, Kenta
Hailemariam, Kiros
Ninomiya-Tsuji, Jun
Tsuji, Yoshiaki
Regulation of Genotoxic Stress Response by Homeodomain-interacting Protein Kinase 2 through Phosphorylation of Cyclic AMP Response Element-binding Protein at Serine 271
title Regulation of Genotoxic Stress Response by Homeodomain-interacting Protein Kinase 2 through Phosphorylation of Cyclic AMP Response Element-binding Protein at Serine 271
title_full Regulation of Genotoxic Stress Response by Homeodomain-interacting Protein Kinase 2 through Phosphorylation of Cyclic AMP Response Element-binding Protein at Serine 271
title_fullStr Regulation of Genotoxic Stress Response by Homeodomain-interacting Protein Kinase 2 through Phosphorylation of Cyclic AMP Response Element-binding Protein at Serine 271
title_full_unstemmed Regulation of Genotoxic Stress Response by Homeodomain-interacting Protein Kinase 2 through Phosphorylation of Cyclic AMP Response Element-binding Protein at Serine 271
title_short Regulation of Genotoxic Stress Response by Homeodomain-interacting Protein Kinase 2 through Phosphorylation of Cyclic AMP Response Element-binding Protein at Serine 271
title_sort regulation of genotoxic stress response by homeodomain-interacting protein kinase 2 through phosphorylation of cyclic amp response element-binding protein at serine 271
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921112/
https://www.ncbi.nlm.nih.gov/pubmed/20573984
http://dx.doi.org/10.1091/mbc.E10-01-0015
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