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HIPK family kinases bind and regulate the function of the CCR4-NOT complex

The serine/threonine kinase HIPK2 functions as a regulator of developmental processes and as a signal integrator of a wide variety of stress signals, such as DNA damage, hypoxia, and reactive oxygen intermediates. Because the kinase is generated in a constitutively active form, its expression levels...

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Autores principales: Rodriguez-Gil, Alfonso, Ritter, Olesja, Hornung, Juliane, Stekman, Hilda, Krüger, Marcus, Braun, Thomas, Kremmer, Elisabeth, Kracht, Michael, Schmitz, M. Lienhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907730/
https://www.ncbi.nlm.nih.gov/pubmed/27122605
http://dx.doi.org/10.1091/mbc.E15-09-0629
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author Rodriguez-Gil, Alfonso
Ritter, Olesja
Hornung, Juliane
Stekman, Hilda
Krüger, Marcus
Braun, Thomas
Kremmer, Elisabeth
Kracht, Michael
Schmitz, M. Lienhard
author_facet Rodriguez-Gil, Alfonso
Ritter, Olesja
Hornung, Juliane
Stekman, Hilda
Krüger, Marcus
Braun, Thomas
Kremmer, Elisabeth
Kracht, Michael
Schmitz, M. Lienhard
author_sort Rodriguez-Gil, Alfonso
collection PubMed
description The serine/threonine kinase HIPK2 functions as a regulator of developmental processes and as a signal integrator of a wide variety of stress signals, such as DNA damage, hypoxia, and reactive oxygen intermediates. Because the kinase is generated in a constitutively active form, its expression levels are restricted by a variety of different mechanisms. Here we identify the CCR4-NOT complex as a new regulator of HIPK2 abundance. Down-regulation or knockout of the CCR4-NOT complex member CNOT2 leads to reduced HIPK2 protein levels without affecting the expression level of HIPK1 or HIPK3. A fraction of all HIPK family members associates with the CCR4-NOT components CNOT2 and CNOT3. HIPKs also phosphorylate the CCR4-NOT complex, a feature that is shared with their yeast progenitor kinase, YAK1. Functional assays reveal that HIPK2 and HIPK1 restrict CNOT2-dependent mRNA decay. HIPKs are well known regulators of transcription, but the mutual regulation between CCR4-NOT and HIPKs extends the regulatory potential of these kinases by enabling posttranscriptional gene regulation.
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spelling pubmed-49077302016-08-30 HIPK family kinases bind and regulate the function of the CCR4-NOT complex Rodriguez-Gil, Alfonso Ritter, Olesja Hornung, Juliane Stekman, Hilda Krüger, Marcus Braun, Thomas Kremmer, Elisabeth Kracht, Michael Schmitz, M. Lienhard Mol Biol Cell Articles The serine/threonine kinase HIPK2 functions as a regulator of developmental processes and as a signal integrator of a wide variety of stress signals, such as DNA damage, hypoxia, and reactive oxygen intermediates. Because the kinase is generated in a constitutively active form, its expression levels are restricted by a variety of different mechanisms. Here we identify the CCR4-NOT complex as a new regulator of HIPK2 abundance. Down-regulation or knockout of the CCR4-NOT complex member CNOT2 leads to reduced HIPK2 protein levels without affecting the expression level of HIPK1 or HIPK3. A fraction of all HIPK family members associates with the CCR4-NOT components CNOT2 and CNOT3. HIPKs also phosphorylate the CCR4-NOT complex, a feature that is shared with their yeast progenitor kinase, YAK1. Functional assays reveal that HIPK2 and HIPK1 restrict CNOT2-dependent mRNA decay. HIPKs are well known regulators of transcription, but the mutual regulation between CCR4-NOT and HIPKs extends the regulatory potential of these kinases by enabling posttranscriptional gene regulation. The American Society for Cell Biology 2016-06-15 /pmc/articles/PMC4907730/ /pubmed/27122605 http://dx.doi.org/10.1091/mbc.E15-09-0629 Text en © 2016 Rodriguez-Gil, Ritter, Hornung, 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 for Cell Biology.
spellingShingle Articles
Rodriguez-Gil, Alfonso
Ritter, Olesja
Hornung, Juliane
Stekman, Hilda
Krüger, Marcus
Braun, Thomas
Kremmer, Elisabeth
Kracht, Michael
Schmitz, M. Lienhard
HIPK family kinases bind and regulate the function of the CCR4-NOT complex
title HIPK family kinases bind and regulate the function of the CCR4-NOT complex
title_full HIPK family kinases bind and regulate the function of the CCR4-NOT complex
title_fullStr HIPK family kinases bind and regulate the function of the CCR4-NOT complex
title_full_unstemmed HIPK family kinases bind and regulate the function of the CCR4-NOT complex
title_short HIPK family kinases bind and regulate the function of the CCR4-NOT complex
title_sort hipk family kinases bind and regulate the function of the ccr4-not complex
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907730/
https://www.ncbi.nlm.nih.gov/pubmed/27122605
http://dx.doi.org/10.1091/mbc.E15-09-0629
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