HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 4, 2215-2224, January 27, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/4/2215    most recent M509509200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, S.-J. Articles by Kim, K.-T. Search for Related Content PubMed PubMed Citation Articles by Lee, S.-J. Articles by Kim, K.-T. Social Bookmarking                      What's this?

Regulation of p53 by Activated Protein Kinase C- during Nitric Oxide-induced Dopaminergic Cell Death^*

Sung-Jin Lee, Dong-Chan Kim, Bo-Hwa Choi, Hyunjung Ha, and Kyong-Tai Kim1

From the Systems Bio-Dynamics NCRC, Division of Molecular and Life Science, POSTECH, Pohang, 790-784 and the Department of Biochemistry, School of Life Sciences, Chungbuk National University, Cheongju, 361-763, Korea

Selective cell death of dopaminergic neurons in the substantia nigra is the major cause of Parkinson disease. Current evidence suggests that this cell death could be mediated by nitric oxide by-products such as nitrate and peroxynitrite. Because protein kinase C (PKC)- is implicated in apoptosis of various cell types, we studied its roles and activation mechanisms in nitric oxide (NO)-induced apoptosis of SN4741 dopaminergic cells. When cells were treated with sodium nitroprusside (SNP), a NO donor, endogenous PKC- was nitrated and activated. Immunoprecipitation revealed that p53 co-immunoprecipitated with PKC- and was phosphorylated at the 15th serine residue in SNP-treated cells. An in vitro kinase assay revealed that p53 was directly phosphorylated by SNP-activated PKC-. The p53 Ser-15 phosphorylation was suppressed in SNP-treated cells when the NO-mediated activation of PKC- was inhibited by rottlerin or (-)-epigallocatechin gallate. Within 3 h of p53 phosphorylation, its protein levels increased because of decreased ubiquitin-dependent proteosomal proteolysis, whereas the protein levels of MDM2, ubiquitin-protein isopeptide ligase, were down-regulated in a p53 phosphorylation-dependent fashion. Taken together, these results demonstrate that nitration-mediated activation of PKC- induces the phosphorylation of the Ser-15 residue in p53, which increases its protein stability, thereby contributing to the nitric oxide-mediated apoptosis-like cell death pathway. These findings may be expanded to provide new insight into the cellular mechanisms of Parkinson disease.

Received for publication, August 29, 2005 , and in revised form, November 7, 2005.

^* This work was supported by the Brain Neurobiology Research Program Grant M10412000088-04N1200-08810 and Systems Bio-Dynamics National Core Research Center sponsored by the Korean Ministry of Science and Technology and Brain Korea 21 Program of the Korean Ministry of Education. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Life Science, Division of Molecular and Life Science, POSTECH, Pohang, 790-784, Korea. Tel.: 82-54-279-2297; Fax: 82-54-279-2199; E-mail: ktk{at}postech.ac.kr.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Sandoval, M. Morales, R. Tapia, L. del Carmen Alarcon, M. Sordo, P. Ostrosky-Wegman, A. Ortega, and E. Lopez-Bayghen p53 Response to Arsenic Exposure in Epithelial Cells: Protein Kinase B/Akt Involvement Toxicol. Sci., September 1, 2007; 99(1): 126 - 140. [Abstract] [Full Text] [PDF]

				J.-H. Lee, H.-S. Kim, S.-J. Lee, and K.-T. Kim Stabilization and activation of p53 induced by Cdk5 contributes to neuronal cell death J. Cell Sci., July 1, 2007; 120(13): 2259 - 2271. [Abstract] [Full Text] [PDF]

				M. Gareskog and P. Wentzel N-Acetylcysteine and {alpha}-cyano-4-hydroxycinnamic acid alter protein kinase C (PKC)-{delta} and PKC-{zeta} and diminish dysmorphogenesis in rat embryos cultured with high glucose in vitro J. Endocrinol., January 1, 2007; 192(1): 207 - 214. [Abstract] [Full Text] [PDF]