Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2
AuthorsKovács, Krisztián A.
Magistretti, Pierre J.
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/594104
MetadataShow full item record
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.
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.
SponsorsResearch Executive Agency
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung[31003A-135692, 3100A0-105773, 3100A0-120699]
- Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2.
- Authors: Hofmann TG, Möller A, Sirma H, Zentgraf H, Taya Y, Dröge W, Will H, Schmitz ML
- Issue date: 2002 Jan
- Regulation of genotoxic stress response by homeodomain-interacting protein kinase 2 through phosphorylation of cyclic AMP response element-binding protein at serine 271.
- Authors: Sakamoto K, Huang BW, Iwasaki K, Hailemariam K, Ninomiya-Tsuji J, Tsuji Y
- Issue date: 2010 Aug 15
- Phosphorylation of ETS transcription factor ER81 in a complex with its coactivators CREB-binding protein and p300.
- Authors: Papoutsopoulou S, Janknecht R
- Issue date: 2000 Oct
- Roles of HIPK1 and HIPK2 in AML1- and p300-dependent transcription, hematopoiesis and blood vessel formation.
- Authors: Aikawa Y, Nguyen LA, Isono K, Takakura N, Tagata Y, Schmitz ML, Koseki H, Kitabayashi I
- Issue date: 2006 Sep 6
- Arsenic-Induced Activation of the Homeodomain-Interacting Protein Kinase 2 (HIPK2) to cAMP-Response Element Binding Protein (CREB) Axis.
- Authors: Hashimoto K, Tsuji Y
- Issue date: 2017 Jan 6