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

Qinghong Zhang, Yasuhiro Yoshimatsu, Jeffrey Hildebrand, Steven M. Frisch, Richard H. Goodman

Research output: Contribution to journalArticlepeer-review

196 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)177-186
Number of pages10
JournalCell
Volume115
Issue number2
DOIs
StatePublished - Oct 17 2003

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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