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

J. Biol. Chem., Vol. 278, Issue 16, 14299-14305, April 18, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/16/14299    most recent M211699200v1 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 Ofek, P. Articles by Lavi, S. Search for Related Content PubMed PubMed Citation Articles by Ofek, P. Articles by Lavi, S. Social Bookmarking                      What's this?

Cell Cycle Regulation and p53 Activation by Protein Phosphatase 2C^*

Paula Ofek, Daniella Ben-Meir, Zehavit Kariv-Inbal, Moshe Oren^§, and Sara Lavi^¶

From the  Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv 69978, Israel and ^§ Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel

Protein phosphatase 2C (PP2C) dephosphorylates a broad range of substrates, regulating stress response and growth-related pathways in both prokaryotes and eukaryotes. We now demonstrate that PP2C, a major mammalian isoform, inhibits cell growth and activates the p53 pathway. In 293 cell clones, in which PP2C expression is regulated by a tetracycline-inducible promoter, PP2C overexpression led to G₂/M cell cycle arrest and apoptosis. Furthermore, PP2C induced the expression of endogenous p53 and the p53-responsive gene p21. Activation of the p53 pathway by PP2C took place both in cells harboring endogenous p53, as well as in p53-null cells transfected with exogenous p53. Induction of PP2C resulted in an increase in the overall levels of p53 protein as well as an augmentation of p53 transcription activity. The dephosphorylation activity of PP2C is essential to the described phenomena, as none of these effects was detected when an enzymatically inactive PP2C mutant was overexpressed. p53 plays an important role in PP2C-directed cell cycle arrest and apoptosis because perturbation of p53 expression in human 293 cells by human papillomavirus E6 led to a significant increase in cell survival. The role of PP2C in p53 activation is discussed.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. Yan, Y. Song, C. P. Wong, K. Hardin, and E. Ho Zinc Deficiency Alters DNA Damage Response Genes in Normal Human Prostate Epithelial Cells J. Nutr., April 1, 2008; 138(4): 667 - 673. [Abstract] [Full Text] [PDF]

				T. Bonome, J.-Y. Lee, D.-C. Park, M. Radonovich, C. Pise-Masison, J. Brady, G. J. Gardner, K. Hao, W. H. Wong, J. C. Barrett, et al. Expression Profiling of Serous Low Malignant Potential, Low-Grade, and High-Grade Tumors of the Ovary Cancer Res., November 15, 2005; 65(22): 10602 - 10612. [Abstract] [Full Text] [PDF]

				B. P. Harvey, S. S. Banga, and H. L. Ozer Regulation of the Multifunctional Ca2+/Calmodulin-dependent Protein Kinase II by the PP2C Phosphatase PPM1F in Fibroblasts J. Biol. Chem., June 4, 2004; 279(23): 24889 - 24898. [Abstract] [Full Text] [PDF]