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Rodriguez-Gil, A.* ; Ritter, O.* ; Hornung, J.* ; Stekman, H.* ; Krüger, M.* ; Braun, T.* ; Kremmer, E. ; Kracht, M.* ; Schmitz, M.L.*

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

Mol. Biol. Cell 27, 1969-1980 (2016)
Verlagsversion Postprint DOI PMC
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter 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
Zeitschrift Molecular Biology of the Cell
Quellenangaben Band: 27, Heft: 12, Seiten: 1969-1980 Artikelnummer: , Supplement: ,
Verlag American Society for Cell Biology (ASCB)
Verlagsort Bethesda
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)