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

Handle URI:
http://hdl.handle.net/10754/594104
Title:
Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2
Authors:
Kovács, Krisztián A.; Steinmann, Myriam; Halfon, Olivier; Magistretti, Pierre J. ( 0000-0002-6678-320X ) ; Cardinaux, Jean René
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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
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.
Publisher:
Elsevier BV
Journal:
Cellular Signalling
Issue Date:
Nov-2015
DOI:
10.1016/j.cellsig.2015.08.001
PubMed ID:
26247811
Type:
Article
ISSN:
0898-6568
Sponsors:
Research Executive Agency[291734]; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung[31003A-135692, 3100A0-105773, 3100A0-120699]
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorKovács, Krisztián A.en
dc.contributor.authorSteinmann, Myriamen
dc.contributor.authorHalfon, Olivieren
dc.contributor.authorMagistretti, Pierre J.en
dc.contributor.authorCardinaux, Jean Renéen
dc.date.accessioned2016-01-19T13:21:44Zen
dc.date.available2016-01-19T13:21:44Zen
dc.date.issued2015-11en
dc.identifier.citationKovács 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.en
dc.identifier.issn0898-6568en
dc.identifier.pmid26247811en
dc.identifier.doi10.1016/j.cellsig.2015.08.001en
dc.identifier.urihttp://hdl.handle.net/10754/594104en
dc.description.abstractCREB-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.en
dc.description.sponsorshipResearch Executive Agency[291734]en
dc.description.sponsorshipSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung[31003A-135692, 3100A0-105773, 3100A0-120699]en
dc.publisherElsevier BVen
dc.subjectCBPen
dc.subjectCoactivatoren
dc.subjectHIPK2en
dc.subjectProtein kinaseen
dc.subjectTranscriptional regulationen
dc.titleComplex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2en
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalCellular Signallingen
dc.contributor.institutionCenter for Psychiatric Neuroscience, Department of Psychiatry, University Medical Center, University of Lausanne, Prilly, Switzerlanden
dc.contributor.institutionService of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Lausanne, Switzerlanden
dc.contributor.institutionInstitute of Science and Technology, Klosterneuburg, Austriaen
dc.contributor.institutionLaboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerlanden
dc.contributor.institutionNestlé Research Center, Vers-chez-les-Blanc, 1000 Lausanne 26, Switzerlanden
kaust.authorMagistretti, Pierre J.en

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