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Mol Cell Biol

Title:		The transcriptional repressor ZEB regulates p73 expression at the crossroad between proliferation and differentiation
Author(s):		Fontemaggi G; Gurtner A; Strano S; Higashi Y; Sacchi A; Piaggio G; Blandino G;
Address:		"Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Via delle Messe d'Oro, 156, 00158 Rome, Italy"
Journal Title:		Mol Cell Biol
Year:		2001
Volume:		21
Issue:		24
Page Number:		8461 - 8470
DOI:		10.1128/MCB.21.24.8461-8470.2001
ISSN/ISBN:		0270-7306 (Print) 1098-5549 (Electronic) 0270-7306 (Linking)
Abstract:		"The newly discovered p73 gene encodes a nuclear protein that has high homology with p53. Furthermore, ectopic expression of p73 in p53(+/+) and p53(-/-) cancer cells recapitulates some of the biological activities of p53 such as growth arrest, apoptosis, and differentiation. p73(-/-)-deficient mice exhibit severe defects in proper development of the central nervous system and pheromone sensory pathway. They also suffer from inflammation and infections. Here we studied the transcriptional regulation of p73 at the crossroad between proliferation and differentiation. p73 mRNA is undetectable in proliferating C2C12 cells and is expressed at very low levels in undifferentiated P19 and HL60 cells. Conversely, it is upregulated during muscle and neuronal differentiation as well as in response to tetradecanoyl phorbol acetate-induced monocytic differentiation of HL60 cells. We identified a 1-kb regulatory fragment located within the first intron of p73, which is positioned immediately upstream to the ATG codon of the second exon. This fragment exerts silencer activity on p73 as well as on heterologous promoters. The p73 intronic fragment contains six consensus binding sites for transcriptional repressor ZEB, which binds these sites in vitro and in vivo. Ectopic expression of dominant-negative ZEB (ZEB-DB) restores p73 expression in proliferating C2C12 and P19 cells. Thus, transcriptional repression of p73 expression by ZEB binding may contribute to the modulation of p73 expression during differentiation"
Keywords:		"Animals Apoptosis Base Sequence Binding Sites Blotting, Western Cell Differentiation Cell Division Cell Line Cell Nucleus/metabolism Cells, Cultured Chromatin/metabolism Cloning, Molecular Codon DNA-Binding Proteins/*metabolism Exons Genes, Dominant Genes;"
Notes:		"MedlineFontemaggi, G Gurtner, A Strano, S Higashi, Y Sacchi, A Piaggio, G Blandino, G eng Research Support, Non-U.S. Gov't 2001/11/20 Mol Cell Biol. 2001 Dec; 21(24):8461-70. doi: 10.1128/MCB.21.24.8461-8470.2001"