Science and Research

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 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.

  • Rodriguez-Gil, A.; Ritter, O.; Hornung, J.; Stekman, H.; Kruger, M.; Braun, T.; Kremmer, E.; Kracht, M.; Schmitz, M. L.
Publication details
DOI: 10.1091/mbc.E15-09-0629
Journal: Molecular biology of the cell
Pages: 1969-80 
Number: 12
Work Type: Original
Location: UGMLC
Disease Area: General Lung and Other
Partner / Member: JLU, MPI-BN
Access-Number: 27122605
See publication on PubMed

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