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Molecular and Cellular Biology, February 2004, p. 1132-1142, Vol. 24, No. 3
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.3.1132-1142.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Tumor Suppressor p53 Inhibits Net, an Effector of Ras/Extracellular Signal-Regulated Kinase Signaling

Koji Nakade, Hong Zheng, Gitali Ganguli, Gilles Buchwalter, Christian Gross, and Bohdan Wasylyk^*

Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 67404 Illkirch cedex, France

Received 30 June 2003/ Returned for modification 11 August 2003/ Accepted 6 November 2003

The tumor suppressor function of p53 is linked to its ability to repress gene expression, but the mechanisms of specific gene repression are poorly understood. We report that wild-type p53 inhibits an effector of the Ras oncogene/mitogen-activated protein (MAP) kinase pathway, the transcription factor Net. Tumor-associated mutant p53s are less efficient inhibitors. p53 inhibits by preventing phosphorylation of Net by MAP kinases. Loss of p53 in vivo leads to increased Net phosphorylation in response to wound healing and UV irradiation of skin. Our results show that p53 can repress specific gene expression by inhibiting Net, a factor implicated in cell cycle entry.

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* Corresponding author. Mailing address: Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, BP 10142, 67404 Illkirch cedex, France. Phone: 33 3 88 65 34 11. Fax: 33 3 88 65 32 01. E-mail: boh{at}igbmc.u-strasbg.fr.

H.Z. and G.G. contributed equally to this report.

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Molecular and Cellular Biology, February 2004, p. 1132-1142, Vol. 24, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.3.1132-1142.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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