Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2 Journal Article

Author(s): Kovács, Krisztián A; Steinmann, Myriam; Halfon, Olivier; Magistretti, Pierre J; Cardinaux, Jean-René
Article Title: Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2
Affiliation IST Austria
Abstract: CREB-binding protein (CBP) and p300 are transcriptional coactivators involved in numerous biological processes that affect cell growth, transformation, differentiation, and development. In this study, we provide evidence of the involvement of homeodomain-interacting protein kinase 2 (HIPK2) in the regulation of CBP activity. We show that HIPK2 interacts with and phosphorylates several regions of CBP. We demonstrate that serines 2361, 2363, 2371, 2376, and 2381 are responsible for the HIPK2-induced mobility shift of CBP C-terminal activation domain. Moreover, we show that HIPK2 strongly potentiates the transcriptional activity of CBP. However, our data suggest that HIPK2 activates CBP mainly by counteracting the repressive action of cell cycle regulatory domain 1 (CRD1), located between amino acids 977 and 1076, independently of CBP phosphorylation. Our findings thus highlight a complex regulation of CBP activity by HIPK2, which might be relevant for the control of specific sets of target genes involved in cellular proliferation, differentiation and apoptosis.
Keywords: protein kinase; Transcriptional regulation; Coactivator; CBP; HIPK2
Journal Title: Cellular Signalling
Volume: 27
Issue 11
ISSN: 0898-6568
Publisher: Elsevier  
Date Published: 2015-11-01
Start Page: 2252
End Page: 2260
DOI: 10.1016/j.cellsig.2015.08.001
Notes: This work was supported by Swiss National Science Foundation Grants 3100A0-105773, 3100A0-120699, and 31003A-135692 to J-R. C., and partly by an IST Fellowship awarded to K. A. K. (Project: P IST EU01 under REA grant agreement no. 291734). We thank Silvia Soddu for the pCMV-HIPK2-FLAG expression vector.
Open access: yes (repository)