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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
Identification of Direct p73 Target Genes Combining DNA
Microarray and Chromatin Immunoprecipitation Analyses*
Giulia
Fontemaggi §,
Itai
Kela¶ ,
Ninette
Amariglio**,
Gideon
Rechavi** ,
Janakiraman
Krishnamurthy§§,
Sabrina
Strano ,
Ada
Sacchi ,
David
Givol§§, and
Giovanni
Blandino ¶¶
From the 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 p73 or p53 activation using oligonucleotide microarrays capable of detecting ~11,000 mRNA species. Our results indicate that p73 and p53 activate both common and distinct groups of genes. We found 141 and 320 genes
whose expression is modulated by p73 and p53,
respectively. p73 up-regulates 85 genes, whereas p53 induces 153 genes, of which 27 are in common with p73 . 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 p73 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.

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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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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