Article abstract
Nature Cell Biology 4, 1 - 10 (2001)
Published online: 10 December 2001 | doi:10.1038/ncb715
Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2
Thomas G. Hofmann1,2, Andreas Möller1, Hüseyin Sirma2, Hanswalter Zentgraf3, Yoichi Taya4, Wulf Dröge1, Hans Will2 & M. Lienhard Schmitz1,5
Abstract
Transcriptional activity of p53, a central regulatory switch in a network controlling cell proliferation and apoptosis, is modulated by protein stability and post-translational modifications including phosphorylation and acetylation. Here we demonstrate that the human serine/threonine kinase homeodomain-interacting protein kinase-2 (HIPK2) colocalizes and interacts with p53 and CREB-binding protein (CBP) within promyelocytic leukaemia (PML) nuclear bodies. HIPK2 is activated by ultraviolet (UV) radiation and selectively phosphorylates p53 at Ser 46, thus facilitating the CBP-mediated acetylation of p53 at Lys 382, and promoting p53-dependent gene expression. Accordingly, the kinase function of HIPK2 mediates the increased expression of p53 target genes, which results in growth arrest and the enhancement of UV-induced apoptosis. Interference with HIPK2 expression by antisense oligonucleotides impairs UV-induced apoptosis. Our results imply that HIPK2 is a novel regulator of p53 effector functions involved in cell growth, proliferation and apoptosis.
- Division of Immunochemistry (G0200) German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
- Department of General Virology, Heinrich-Pette-Institut für experimentelle Virologie und Immunologie, Martinistrasse 52, 20251 Hamburg, Germany
- Division of Applied Tumour Virology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
- Radiobiology Division, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan
- Current address: Department for Chemistry and Biochemistry, Freiestrasse 3 CH-3012, Bern, Switzerland
Correspondence to: M. Lienhard Schmitz1,5 e-mail: L.Schmitz@DKFZ.de
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