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HIPK family kinases bind and regulate the function of the CCR4-NOT complex.
Mol. Biol. Cell 27, 1969-1980 (2016)
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. As 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. Downregulation or knockout of the CCR4-NOT complex member CNOT2 leads to reduced HIPK2 protein levels without affecting the expression levels 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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Interacting Protein Kinase-2; Rna-polymerase-ii; Nf-kappa-b; Messenger-rna; Saccharomyces-cerevisiae; Dna-damage; Subcellular-localization; Translational Repression; Catalytic-activity; Activation-loop
ISSN (print) / ISBN
1059-1524
e-ISSN
1939-4586
Journal
Molecular Biology of the Cell
Quellenangaben
Volume: 27,
Issue: 12,
Pages: 1969-1980
Publisher
American Society for Cell Biology (ASCB)
Publishing Place
Bethesda
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Immunology (IMI)