QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 1 March 2005
doi: 10.1242/jcs.01704

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.01704v1 118/6/1245    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goldschneider, D. Articles by Douc-Rasy, S. Search for Related Content PubMed PubMed Citation Articles by Goldschneider, D. Articles by Douc-Rasy, S.

The neurogene BTG2^TIS21/PC3 is transactivated by Np73 via p53 specifically in neuroblastoma cells

David Goldschneider¹, Karine Million¹, Anne Meiller³, Hedi Haddada¹, Alain Puisieux², Jean Bénard¹, Evelyne May^3,* and Sétha Douc-Rasy^1,

¹ CNRS UMR 8126, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94800 Villejuif, France
² INSERM U590, Centre Leon Bérard, 28 rue Laënnec, 69008 Lyon, France
³ CEA-CNRS UMR217, PB6, 92265 Fontenay-aux-Roses, France

Author for correspondence (e-mail: sdouc{at}igr.fr)

Accepted 6 January 2005

The p53 gene and its homologue p73 are rarely mutated in neuroblastoma. In recent studies, we showed that overexpression of Np73, an isoform lacking the N-terminal transactivation (TA) domain, surprisingly induces p53 protein accumulation in the wild-type (wt) p53 human neuroblastoma line SH-SY5Y. As can be expected owing to its dominant-negative effect, Np73 inhibits Waf1/p21 gene expression, but equally importantly, it upregulates BTG2^TIS21/PC3, another p53 target gene. This effect is not observed in neuroblastoma cells that express a mutated p53. To better understand the Np73-mediated transactivation of the BTG2^TIS21/PC3 gene we performed luciferase assays with two reporter plasmids harboring long and short BTG2 promoter sequences in three human neuroblastoma cell lines and one breast cancer cell line. Our results demonstrate that BTG2^TIS21/PC3 transactivation by Np73 depends on both p53 status (as it is not observed in a p53^–/– neuroblastoma cell line) and cellular context (as it occurs in a p53^+/+ neuroblastoma cell line but not in a p53^+/+ breast tumor cell line). The fact that Np73 may either inhibit or stimulate wt-p53 transcriptional activity, depending on both the p53 target gene and the cellular context, was confirmed by real-time quantitative PCR. Moreover, transactivation of the BTG2^TIS21/PC3 promoter requires a complete Np73 C-terminus sequence as it is not observed with Np73ß, which lacks most of the C-terminal domain. We have previously shown that Np73 is the only p73 isoform expressed in undifferentiated neuroblastoma tumors. In light of all these findings, we propose that Np73 not only acts as an inhibitor of p53/TAp73 functions in neuroblastoma tumors, but also cooperates with wt-p53 in playing a physiological role through the activation of BTG2^TIS21/PC3 gene expression.

Key words: p73, p53, BTG2^TIS21/PC3, Transactivation, Neuroblastoma, Apoptosis, Differentiation, Development

This article has been cited by other articles:

				E. Horvilleur, M. Bauer, D. Goldschneider, X. Mergui, A. de La Motte, J. Benard, S. Douc-Rasy, and D. Cappellen p73{alpha} isoforms drive opposite transcriptional and post-transcriptional regulation of MYCN expression in neuroblastoma cells Nucleic Acids Res., August 1, 2008; 36(13): 4222 - 4232. [Abstract] [Full Text] [PDF]

				J. Zhang and X. Chen {Delta}Np73 Modulates Nerve Growth Factor-Mediated Neuronal Differentiation through Repression of TrkA Mol. Cell. Biol., May 15, 2007; 27(10): 3868 - 3880. [Abstract] [Full Text] [PDF]

				D. Goldschneider, E. Horvilleur, L.-F. Plassa, M. Guillaud-Bataille, K. Million, E. Wittmer-Dupret, G. Danglot, H. d. The, J. Benard, E. May, et al. Expression of C-terminal deleted p53 isoforms in neuroblastoma Nucleic Acids Res., November 14, 2006; 34(19): 5603 - 5612. [Abstract] [Full Text] [PDF]

				J.-C. Bourdon, K. Fernandes, F. Murray-Zmijewski, G. Liu, A. Diot, D. P. Xirodimas, M. K. Saville, and D. P. Lane p53 isoforms can regulate p53 transcriptional activity Genes & Dev., September 15, 2005; 19(18): 2122 - 2137. [Abstract] [Full Text] [PDF]