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PMID: 12628935 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Protein kinase Cdelta is responsible for constitutive and DNA damage-induced phosphorylation of Rad9.

The EMBO journal ·Vol. 22 ·No. 6 ·2003-03-17 ·Pages 1431-41

Yoshida K, Wang HG, Miki Y, Kufe D

Abstract

The mammalian homolog of the Schizosaccharomyces pombe Rad9 is involved in checkpoint signaling and the induction of apoptosis. While the mechanisms responsible for the regulation of human Rad9 (hRad9) are not known, hRad9 is subject to hyperphosphorylation in the response of cells to DNA damage. The present results demonstrate that protein kinase Cdelta (PKCdelta) associates with Rad9 and that DNA damage induces this interaction. PKCdelta phosphorylates hRad9 in vitro and in cells exposed to genotoxic agents. The functional significance of the interaction between hRad9 and PKCdelta is supported by the finding that activation of PKCdelta is necessary for formation of the Rad9-Hus1-Rad1 complex. We also show that PKCdelta is required for binding of hRad9 to Bcl-2. In concert with these results, inhibition of PKCdelta attenuates Rad9-mediated apoptosis. These findings demonstrate that PKCdelta is responsible for the regulation of Rad9 in the Hus1-Rad1 complex and in the apoptotic response to DNA damage.

MeSH Terms
Apoptosis Ataxia Telangiectasia Mutated Proteins Cell Cycle Proteins/drug effects,metabolism Cell Death Cell Line Cytarabine/pharmacology DNA Damage DNA-Binding Proteins Enzyme Activation Green Fluorescent Proteins Humans Luminescent Proteins/metabolism Phosphorylation Protein Binding Protein Kinase C/drug effects,metabolism Protein Kinase C-delta Protein Serine-Threonine Kinases/metabolism Proto-Oncogene Proteins c-bcl-2/metabolism RNA, Small Interfering/metabolism Recombinant Proteins/metabolism Tumor Cells, Cultured Tumor Suppressor Proteins U937 Cells
Chemicals
Cell Cycle Proteins DNA-Binding Proteins Luminescent Proteins Proto-Oncogene Proteins c-bcl-2 RNA, Small Interfering Recombinant Proteins Tumor Suppressor Proteins Cytarabine rad9 protein Green Fluorescent Proteins ATM protein, human Ataxia Telangiectasia Mutated Proteins Protein Serine-Threonine Kinases PRKCD protein, human Protein Kinase C Protein Kinase C-delta
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Yoshida Kiyotsugu
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Wang Hong-Gang
Miki Yoshio
Kufe Donald
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdg134
Published
2003-03-17
Pages
1431-41
Language
English
Region
England
NLM ID
8208664
PMCID
PMC151076
Subset
IM
Grants
NCI NIH HHS · CA90315 · United States
NCI NIH HHS · CA29431 · United States
NCI NIH HHS · R01 CA029431 · United States
NCI NIH HHS · CA55241 · United States
NCI NIH HHS · R01 CA090315 · United States
External Links
PubMed source DOI: 10.1093/emboj/cdg134 PMC Full Text View journal details
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