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 language | English (US) |
|---|---|
| Pages (from-to) | 2802-2807 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 102 |
| Issue number | 8 |
| DOIs | |
| State | Published - Feb 22 2005 |
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ASJC Scopus subject areas
- Genetics
- General
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Homeodomain-interacting protein kinase-2 mediates CtBP phosphorylation and degradation in UV-triggered apoptosis. / Zhang, Qinghong; Nottke, Amanda; Goodman, Richard.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 8, 22.02.2005, p. 2802-2807.Research output: Contribution to journal › Article
}
TY - JOUR
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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U2 - 10.1073/pnas.0409373102
DO - 10.1073/pnas.0409373102
M3 - Article
C2 - 15708980
AN - SCOPUS:14544297432
VL - 102
SP - 2802
EP - 2807
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 8
ER -