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HIPK family kinases bind and regulate the function of the CCR4-NOT complex
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| Zeitschriftentitel: | Molecular Biology of the Cell |
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| Personen und Körperschaften: | , , , , , , , , |
| In: | Molecular Biology of the Cell, 27, 2016, 12, S. 1969-1980 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Cell Biology (ASCB)
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| Schlagwörter: |
| Zusammenfassung: | <jats:p> 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. </jats:p> |
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| Umfang: | 1969-1980 |
| ISSN: |
1059-1524
1939-4586 |
| DOI: | 10.1091/mbc.e15-09-0629 |