|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online December 15, 2003
doi: 10.1242/10.1242/jcs.00834
Research Article |
1 Centre National de la Recherche Scientifique-Unité Mixte de Recherche 8126, 39 rue Camille Desmoulins, 94805 Villejuif, France
2 Institut National de la Santé et de la Recherche Médicale U 362, 39 rue Camille Desmoulins, 94805 Villejuif, France
3 Laboratoire de Génétique, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France
* Author for correspondence (e-mail: sdouc{at}igr.fr)
Accepted 14 August 2003
p73, the first p53 gene homologue, encodes an array of p73 proteins including p73
full-length (TAp73) and amino-truncated isoforms (
Np73), two proteins with opposite biological functions. TAp73 can induce tumor suppressive properties, while Np73 antagonizes p53 as well as TAp73 in a dominant-negative manner. In human malignant neuroblasts, p53 protein is wild-type but known to be excluded from the nucleus, therefore disabling its function as a tumor suppressor. The present study investigates whether there is a functional link between p73 isoforms and p53 in neuroblastoma. Experiments were performed on two neuroblastoma cell lines differing in their p53 status, e.g. wild-type p53 SH-5Y5Y cells and mutated p53 IGR-N-91 cells. Data indicate that (i) both TA- and N-p73 enhance p53 protein level in SH-SY5Y cells, whereas level remains unchanged in IGR-N-91 cells; (ii) only in SH-SY5Y cells does forced TAp73 overexpression markedly induce nuclear accumulation of p53 protein; (iii) p21 protein expression is increased in both cell lines infected with TAp73, suggesting that, in IGR-N-91 cells, p21 is induced by p73 through a p53-independent pathway; (iv) in the SHSY5Y cell line, Btg2 expression is strongly enhanced in cells overexpressing TA, and to a lesser extent in cells overexpressing N. Taken together our results suggest that TAp73 may restore p53 function in NB with wild-type nonfunctional p53, but not in NB with mutated p53.
Key words: Neuroblastoma, p73, p53, Apoptosis, Differentiation
Related articles in JCS:
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]
|
|
|
|
 |
|
 Y. K. Oh, H. J. Lee, M.-H. Jeong, M. Rhee, J.-W. Mo, E. H. Song, J.-Y. Lim, K.-H. Choi, I. Jo, S. I. Park, et al. Role of Activating Transcription Factor 3 on TAp73 Stability and Apoptosis in Paclitaxel-Treated Cervical Cancer Cells Mol. Cancer Res., July 1, 2008; 6(7): 1232 - 1249. [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]
|
|
|
|
 |
|
 D. Goldschneider, K. Million, A. Meiller, H. Haddada, A. Puisieux, J. Benard, E. May, and S. Douc-Rasy The neurogene BTG2TIS21/PC3 is transactivated by {Delta}Np73{alpha} via p53 specifically in neuroblastoma cells J. Cell Sci., March 15, 2005; 118(6): 1245 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Flinterman, L. Guelen, S. Ezzati-Nik, R. Killick, G. Melino, K. Tominaga, J. S. Mymryk, J. Gaken, and M. Tavassoli E1A Activates Transcription of p73 and Noxa to Induce Apoptosis J. Biol. Chem., February 18, 2005; 280(7): 5945 - 5959. [Abstract] [Full Text] [PDF]
|
|
