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

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    Type
    Article
    Authors
    Kovács, Krisztián A.
    Steinmann, Myriam
    Halfon, Olivier
    Magistretti, Pierre J. cc
    Cardinaux, Jean-René cc
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience Program
    Date
    2015-11
    Permanent link to this record
    http://hdl.handle.net/10754/594104
    
    Metadata
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    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. © 2015 Elsevier Inc.
    Citation
    Kovács KA, Steinmann M, Halfon O, Magistretti PJ, Cardinaux J-R (2015) Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2. Cellular Signalling 27: 2252–2260. Available: http://dx.doi.org/10.1016/j.cellsig.2015.08.001.
    Sponsors
    Research Executive Agency[291734]
    Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung[31003A-135692, 3100A0-105773, 3100A0-120699]
    Publisher
    Elsevier BV
    Journal
    Cellular Signalling
    DOI
    10.1016/j.cellsig.2015.08.001
    PubMed ID
    26247811
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.cellsig.2015.08.001
    Scopus Count
    Collections
    Articles; Biological and Environmental Sciences and Engineering (BESE) Division; Bioscience Program

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