Homeodomain-interacting protein kinase-2 mediates CtBP phosphorylation and degradation in UV-triggered apoptosis.

Abstract:

:Homeodomain-interacting protein kinase-2 (HIPK2) is a serine/threonine kinase involved in transcriptional regulation and apoptosis. The transcriptional corepressor CtBP (carboxyl-terminal binding protein) also plays a fundamental role in these processes. Our previous studies indicate that HIPK2 participates in a pathway of UV-triggered CtBP clearance that results in cell death. HIPK2 phosphorylates CtBP at Ser-422 in vitro. We developed a Ser-422 phospho-specific antibody to demonstrate that CtBP is phosphorylated on this residue in response to UV irradiation. HIPK2 knock-down blocked the UV-induced Ser-422 phosphorylation and degradation. The proteasomal inhibitor MG-132 treatment increased levels of ubiquitinated CtBP, which was induced by UV. Interference with HIPK2 function via the kinase-dead mutant decreased CtBP ubiquitination. Furthermore, a phosphopeptide spanning Ser-422 blocked UV-triggered CtBP degradation, confirming that Ser-422 phosphorylation marks CtBP for clearance. Consequently, interference with HIPK2 action in H1299 cells rescued UV-triggered apoptosis.

authors

Zhang Q,Nottke A,Goodman RH

doi

10.1073/pnas.0409373102

keywords:

subject

Has Abstract

pub_date

2005-02-22 00:00:00

pages

2802-7

issue

8

eissn

0027-8424

issn

1091-6490

pii

0409373102

journal_volume

102

pub_type

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