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Molecular and Cellular Biology, October 2004, p. 8529-8540, Vol. 24, No. 19
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.19.8529-8540.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Inhibition of p63 Transcriptional Activity by p14ARF: Functional and Physical Link between Human ARF Tumor Suppressor and a Member of the p53 Family

Viola Calabrò,1,{dagger} Gelsomina Mansueto,1,{dagger} Raffaela Santoro,1 Antonio Gentilella,1 Alessandra Pollice,1 Pamela Ghioni,2 Luisa Guerrini,2 and Girolama La Mantia1*

Department of Genetics, General and Molecular Biology, University of Naples "Federico II," Naples,1 Department of Biomolecular and Biotechnological Sciences, University of Milan, Milan, Italy2

Received 4 March 2004/ Returned for modification 3 April 2004/ Accepted 2 July 2004

The ARF/MDM2/p53 pathway is a principal defense mechanism to protect the organism from uncontrolled effects of deregulated oncogenes. Oncogenes activate ARF, which interacts with and inhibits the ubiquitin ligase MDM2, resulting in p53 stabilization and activation. Once stabilized and activated, p53 can either induce or repress a wide array of different gene targets, which in turn can regulate cell cycle, DNA repair, and a number of apoptosis-related genes. Here we show that, unlike p53, p63, a member of the p53 family, directly interacts with p14ARF. Through this interaction ARF inhibits p63-mediated transactivation and transrepression. In p63-transfected cells, ARF, which normally localizes into nucleoli, accumulates in the nucleoplasm. Based on these observations, we suggest that stimuli inducing p14ARF expression can, at the same time, activate p53 and impair p63 transcriptional activity, altering the pattern of p53 target gene expression. Here we show, for the first time, a physical and functional link between the p14ARF tumor suppressor protein and p63, a member of the p53 family.

* Corresponding author. Mailing address: Department of Genetics, General and Molecular Biology, University of Naples "Federico II," Via Mezzocannone, 8, 80134 Naples, Italy. Phone: 39-081-2535189. Fax: 39-081-2535000. E-mail: lamantia{at}unina.it.

{dagger} V.C. and G.M. contributed equally to this study.

Molecular and Cellular Biology, October 2004, p. 8529-8540, Vol. 24, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.19.8529-8540.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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