title: Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2.
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.
authors.affiliation: Center for Psychiatric Neuroscience, Department of Psychiatry, University Medical Center, University of Lausanne, Prilly, Switzerland; Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Lausanne, Switzerland; Institute of Science and Technology, Klosterneuburg, Austria. Electronic address: Krisztian.Kovacs@ist.ac.at.
authors.forename: Krisztián A
authors.initials: KA
authors.lastname: Kovács
authors.affiliation: Center for Psychiatric Neuroscience, Department of Psychiatry, University Medical Center, University of Lausanne, Prilly, Switzerland; Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Lausanne, Switzerland. Electronic address: Myriam.Steinmann@rdls.nestle.com.
authors.forename: Myriam
authors.initials: M
authors.lastname: Steinmann
authors.affiliation: Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Lausanne, Switzerland. Electronic address: Olivier.Halfon@chuv.ch.
authors.forename: Olivier
authors.initials: O
authors.lastname: Halfon
authors.affiliation: Division of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia; Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Center for Psychiatric Neuroscience, Department of Psychiatry, University Medical Center, University of Lausanne, Prilly, Switzerland. Electronic address: Pierre.Magistretti@epfl.ch.
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Magistretti
authors.affiliation: Center for Psychiatric Neuroscience, Department of Psychiatry, University Medical Center, University of Lausanne, Prilly, Switzerland; Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Lausanne, Switzerland. Electronic address: Jean-Rene.Cardinaux@chuv.ch.
authors.forename: Jean-René
authors.initials: JR
authors.lastname: Cardinaux
mesh_terms: D017209:Apoptosis / Q000235:genetics; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D050881:E1A-Associated p300 Protein; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; C062521:RCC1 protein, human; D015534:Trans-Activators; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: CBP; Coactivator; HIPK2; Protein kinase; Transcriptional regulation