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Originally published In Press as doi:10.1074/jbc.M205573200 on September 3, 2002

J. Biol. Chem., Vol. 277, Issue 45, 43359-43368, November 8, 2002
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Identification of Direct p73 Target Genes Combining DNA Microarray and Chromatin Immunoprecipitation Analyses*

Giulia FontemaggiDagger §, Itai Kela||, Ninette Amariglio**, Gideon Rechavi**Dagger Dagger , Janakiraman Krishnamurthy§§, Sabrina StranoDagger , Ada SacchiDagger , David Givol§§, and Giovanni BlandinoDagger ¶¶

From the Dagger  Department of Experimental Oncology, Regina Elena Cancer Institute, Rome 00158, Italy,  Department of Physics of Complex System Weizmann Institute of Science, Rehovot 76100, Israel, ** Department of Pediatric Hemato-Oncology, The Chaim Sheba Medical Center and Sackler School of Medicine, Tel-Aviv University, Israel, and §§ Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel

The newly discovered p53 family member, p73, has a striking homology to p53 in both sequence and modular structure. Ectopic expression of p73 promotes transcription of p53 target genes and recapitulates the most characterized p53 biological effects such as growth arrest, apoptosis, and differentiation. Unlike p53-deficient mice that develop normally but are subject to spontaneous tumor formation, p73-deficient mice exhibit severe defects in the development of central nervous system and suffer from inflammation but are not prone to tumor development. These phenotypes suggest different biological activities mediated by p53 and p73 that might reflect activation of specific sets of target genes. Here, we have analyzed the gene expression profile of H1299 cells after p73alpha or p53 activation using oligonucleotide microarrays capable of detecting ~11,000 mRNA species. Our results indicate that p73alpha and p53 activate both common and distinct groups of genes. We found 141 and 320 genes whose expression is modulated by p73alpha and p53, respectively. p73alpha up-regulates 85 genes, whereas p53 induces 153 genes, of which 27 are in common with p73alpha . Functional classification of these genes reveals that they are involved in many aspects of cell function ranging from cell cycle and apoptosis to DNA repair. Furthermore, we report that some of the up-regulated genes are directly activated by p73alpha or p53.


* This work was supported in part by Yad Abraham Research Center for Cancer Diagnosis and Therapy at the Weizmann Institute, the Irving Green Alzheimer research fund, Italian Association for Cancer Research, Italian National Research Council, Italian Health Office, and by European Community Grant QLG1-1999-00273.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.

§ Recipient of a fellowship from Fondazione Italiana per la Ricerca sul Cancro.

|| Partially supported by the German-Israel Science Foundation and the Israel Science Foundation.

Dagger Dagger Holds the Gregorio and Dora Shapiro Chair for Hematologic Malignancies, Sackler School of Medicine, Tel Aviv University.

¶¶ To whom correspondence should be addressed: Dept. of Experimental Oncology, Regina Elena Cancer Institute, Via delle Messi d'oro, 156, 00158-Rome, Italy. Tel.: 39-06-52662522; Fax: 39-06-4180526; E-mail: blandino@ifo.it.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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