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

Qinghong Zhang, Amanda Nottke, Richard Goodman

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65 Citations (Scopus)

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 CtSP is phosphorylated on this residue in response to UV irradiation. HIPK2 knockdown 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.

Original languageEnglish (US)
Pages (from-to)2802-2807
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number8
DOIs
StatePublished - Feb 22 2005

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Homeodomain Proteins
Protein Kinases
Proteolysis
Carrier Proteins
Phosphorylation
Apoptosis
Phospho-Specific Antibodies
Co-Repressor Proteins
Phosphopeptides
Protein-Serine-Threonine Kinases
Ubiquitination
Cell Death
Phosphotransferases

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

@article{9b48ce7dcd71496e9374637a5a8d3740,
title = "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 CtSP is phosphorylated on this residue in response to UV irradiation. HIPK2 knockdown 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.",
author = "Qinghong Zhang and Amanda Nottke and Richard Goodman",
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T1 - Homeodomain-interacting protein kinase-2 mediates CtBP phosphorylation and degradation in UV-triggered apoptosis

AU - Zhang, Qinghong

AU - Nottke, Amanda

AU - Goodman, Richard

PY - 2005/2/22

Y1 - 2005/2/22

N2 - 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 CtSP is phosphorylated on this residue in response to UV irradiation. HIPK2 knockdown 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.

AB - 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 CtSP is phosphorylated on this residue in response to UV irradiation. HIPK2 knockdown 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.

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