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

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Ressource 1Download: 26247811.pdf (1947.07 [Ko])
State: Public
Version: Author's accepted manuscript
Secondary document(s)
Download: 26247811AM.pdf (1949.62 [Ko])
State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_17CCEB3C0812
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2.
Journal
Cellular Signalling
Author(s)
Kovács K.A., Steinmann M., Halfon O., Magistretti P.J., Cardinaux J.R.
ISSN
1873-3913 (Electronic)
ISSN-L
0898-6568
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
27
Number
11
Pages
2252-2260
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
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
Apoptosis/genetics, CREB-Binding Protein/genetics, CREB-Binding Protein/metabolism, Carrier Proteins/genetics, Cell Cycle/genetics, Cell Cycle Proteins/genetics, Cell Differentiation/genetics, Cell Line, Cell Proliferation/genetics, E1A-Associated p300 Protein, Guanine Nucleotide Exchange Factors/genetics, HEK293 Cells, Humans, Nuclear Proteins/genetics, Phosphorylation, Protein Binding/genetics, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases/genetics, Trans-Activators/genetics, Transcription, Genetic, Transcriptional Activation/genetics
Pubmed
Web of science
Create date
11/09/2015 10:33
Last modification date
20/08/2019 12:47
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