article published yes Krisztián Kovács author 2AB5821E-F248-11E8-B48F-1D18A9856A87 Myriam Steinmann author Olivier Halfon author Pierre Magistretti author Jean Cardinaux author JoCs department International IST Postdoc Fellowship Programme project 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. https://research-explorer.ista.ac.at/download/1663/5321/IST-2016-578-v1+1_CLS-D-15-00072R1_.pdf application/pdfno https://creativecommons.org/licenses/by-nc-nd/4.0/ Elsevier2015 eng 26247811 00036177750001210.1016/j.cellsig.2015.08.001 27112252 - 2260 Kovács, Krisztián, et al. “Complex Regulation of CREB-Binding Protein by Homeodomain-Interacting Protein Kinase 2.” <i>Cellular Signalling</i>, vol. 27, no. 11, Elsevier, 2015, pp. 2252–60, doi:<a href="https://doi.org/10.1016/j.cellsig.2015.08.001">10.1016/j.cellsig.2015.08.001</a>. Kovács, K., Steinmann, M., Halfon, O., Magistretti, P., &#38; Cardinaux, J. (2015). Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2. <i>Cellular Signalling</i>. Elsevier. <a href="https://doi.org/10.1016/j.cellsig.2015.08.001">https://doi.org/10.1016/j.cellsig.2015.08.001</a> K. Kovács, M. Steinmann, O. Halfon, P. Magistretti, and J. Cardinaux, “Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2,” <i>Cellular Signalling</i>, vol. 27, no. 11. Elsevier, pp. 2252–2260, 2015. Kovács, Krisztián, Myriam Steinmann, Olivier Halfon, Pierre Magistretti, and Jean Cardinaux. “Complex Regulation of CREB-Binding Protein by Homeodomain-Interacting Protein Kinase 2.” <i>Cellular Signalling</i>. Elsevier, 2015. <a href="https://doi.org/10.1016/j.cellsig.2015.08.001">https://doi.org/10.1016/j.cellsig.2015.08.001</a>. K. Kovács, M. Steinmann, O. Halfon, P. Magistretti, J. Cardinaux, Cellular Signalling 27 (2015) 2252–2260. Kovács K, Steinmann M, Halfon O, Magistretti P, Cardinaux J. Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2. <i>Cellular Signalling</i>. 2015;27(11):2252-2260. doi:<a href="https://doi.org/10.1016/j.cellsig.2015.08.001">10.1016/j.cellsig.2015.08.001</a> Kovács K, Steinmann M, Halfon O, Magistretti P, Cardinaux J. 2015. Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2. Cellular Signalling. 27(11), 2252–2260. 16632018-12-11T11:53:20Z2025-09-23T08:19:10Z