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Cell. 2003 Oct 17;115(2):177-86.

Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP.

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1
Vollum Institute, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA. zhangq@ohsu.edu

Abstract

Genetic knockout of the transcriptional corepressor CtBP in mouse embryo fibroblasts upregulates several genes involved in apoptosis. We predicted, therefore, that a propensity toward apoptosis might be regulated through changes in cellular CtBP. To identify pathways involved in this regulation, we screened a mouse embryo cDNA library with an E1A-CtBP complex and identified the homeodomain interacting protein kinase 2 (HIPK2), which had previously been linked to UV-directed apoptosis through its ability to phosphorylate p53. Expression of HIPK2 or exposure to UV irradiation reduced CtBP levels via a proteosome-mediated pathway. The UV effect was prevented by coexpression of kinase-inactive HIPK2 or reduction in HIPK2 levels via siRNA. Mutation of the residue phosphorylated by HIPK2 prevented UV- and HIPK2-directed CtBP clearance. Finally, reduction in CtBP levels, either by genetic knockout or siRNA, promoted apoptosis in p53-deficient cells. These findings provide a pathway for UV-induced apoptosis in cells lacking p53.

PMID:
14567915
DOI:
10.1016/s0092-8674(03)00802-x
[Indexed for MEDLINE]
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