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Originally published In Press as doi:10.1074/jbc.M909370199 on April 27, 2000

J. Biol. Chem., Vol. 275, Issue 27, 20488-20495, July 7, 2000
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The Phosphotyrosyl Phosphatase Activator Gene Is a Novel p53 Target Gene*

Veerle Janssens, Christine Van HoofDagger , Ivo De Baere, Wilfried Merlevede, and Jozef Goris§

From the Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Herestraat 49, B-3000 Leuven, Belgium

The minimal promoter of the phosphotyrosyl phosphatase activator (PTPA) gene, encoding a regulator of protein phosphatase 2A contains two yin-yang 1 (YY1)-binding sites, positively regulating promoter activity. We now describe a role for p53 in the regulation of PTPA expression. Luciferase reporter assays in Saos-2 cells revealed that p53 could down-regulate PTPA promoter activity in a dose-dependent manner, whereas four different p53 mutants could not. The p53-responsive region mapped to the minimal promoter. Overexpression of YY1 reverses the repressive effect of p53, suggesting a functional antagonism between p53 and YY1. The latter does not involve competition for YY1 binding, but rather direct control of YY1 function. Inhibition of PTPA expression by endogenous p53 was demonstrated in UVB-irradiated HepG2 cells, both on the mRNA and protein level. Also basal PTPA levels are higher in p53-negative (Saos-2) versus p53-positive (HepG2, U2OS) cells, suggesting "latent" p53 can control PTPA expression as well. The higher PTPA levels in U2OS cells, programmed to overexpress constitutively a dominant-negative p53 mutant, corroborate this finding. Thus, PTPA expression is negatively regulated by p53 in normal conditions and in conditions where p53 is up-regulated, via an as yet unknown mechanism involving the negative control of YY1.


* This work was supported in part by grants from the "Fonds voor Wetenschappelijk Onderzoek-Vlaanderen," "Geconcerteerde OnderzoekActies" (GOA) van de Vlaamse Gemeenschap, Human Frontier Science Program, and the European Community Biomed2 Cancer Research Program.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Post-doctoral fellow of the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen.

§ To whom correspondence should be addressed. Tel.: 32-16-345-794; Fax: 32-16-345-995; E-mail: jozef.goris@med.kuleuven.ac.be.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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