This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Calabrò, V. Articles by La Mantia, G. Search for Related Content PubMed PubMed Citation Articles by Calabrò, V. Articles by La Mantia, G.

 Previous Article  |  Next Article 

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 p14^ARF: Functional and Physical Link between Human ARF Tumor Suppressor and a Member of the p53 Family

Viola Calabrò,^1, Gelsomina Mansueto,^1, Raffaela Santoro,¹ Antonio Gentilella,¹ Alessandra Pollice,¹ Pamela Ghioni,² Luisa Guerrini,² and Girolama La Mantia^1*

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 p14^ARF. 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 p14^ARF 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 p14^ARF tumor suppressor protein and p63, a member of the p53 family.

V.C. and G.M. contributed equally to this study.

This article has been cited by other articles:

• Caserta, T. M., Kommagani, R., Yuan, Z., Robbins, D. J., Mercer, C. A., Kadakia, M. P. (2006). p63 Overexpression Induces the Expression of Sonic Hedgehog. Mol Cancer Res 4: 759-768 [Abstract] [Full Text]