Siah-1b is a direct transcriptional target of p53:: Identification of the functional p53 responsive element in the siah-1b promoter

被引:69
作者
Fiucci, G
Beaucourt, S
Duflaut, D
Lespagnol, A
Stumptner-Cuvelette, P
Géant, A
Buchwalter, G
Tuynder, M
Susini, L
Lassalle, JM
Wasylyk, C
Wasylyk, B
Oren, M
Amson, R
Telerman, A
机构
[1] Mol Engines Labs, F-75011 Paris, France
[2] Univ Strasbourg 1, CNRS, INSERM, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France
[3] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel
[4] Univ Toulouse 3, CNRS UMR 5550, Lab Ethol & Psychol Anim, F-31062 Toulouse 4, France
关键词
D O I
10.1073/pnas.0400177101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Siah proteins are E3 ubiquitin ligases. They are homologues of the Drosophila seven in absentia (Sina), a protein required for the R7 photoreceptor development. We have previously found that the expression of human siah-1 and its mouse homologue siah-1b are induced by p53 during apoptosis and tumor reversion. So far, no evidence that the siah-1b gene is a direct transcriptional target of p53 has been provided. In the present study we investigate this issue. Northern blot analysis with a specific probe demonstrates an increase in siah-1b transcription on activation of endogenous and inducible exogenous p53. To explore whether this effect is directly mediated by p53 we analyzed 20 kb of chromosome X DNA, containing the siah-1b locus. A p53-binding site was identified in the siah-1b promoter, located at nucleotides -2155/-2103 relative to the translational start site. This site is composed of two half-sites, conforming to the p53-binding consensus sequence but separated by a nonclassical 33-bp spacer. In luciferase assays, p53 induces a substantial increase in siah-1b promoter activity. Gel shift and DNase-I-footprinting studies, combined with mutational analysis and chromatin immunoprecipitation, indicate that p53 effectively binds the siah-1b promoter in vitro and in vivo. Thus, the siah-1b gene is a direct transcriptional target of p53.
引用
收藏
页码:3510 / 3515
页数:6
相关论文
共 52 条
[1]   Isolation of 10 differentially expressed cDNAs in p53-induced apoptosis: Activation of the vertebrate homologue of the Drosophila seven in absentia gene [J].
Amson, RB ;
Nemani, M ;
Roperch, JP ;
Israeli, D ;
Bougueleret, L ;
LeGall, I ;
Medhioub, M ;
LinaresCruz, G ;
Lethrosne, F ;
Pasturaud, P ;
Piouffre, L ;
Prieur, S ;
Susini, L ;
Alvaro, V ;
Millasseau, P ;
Guidicelli, C ;
Bui, H ;
Massart, C ;
Cazes, L ;
Dufour, F ;
BruzzoniGiovanelli, H ;
Owadi, H ;
Hennion, C ;
Charpak, G ;
Dausset, J ;
Calvo, F ;
Oren, M ;
Cohen, D ;
Telerman, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (09) :3953-3957
[2]   Transcription abnormalities potentiate apoptosis of normal human fibroblasts [J].
Andera, L ;
Wasylyk, B .
MOLECULAR MEDICINE, 1997, 3 (12) :852-863
[3]   SIAH-1 inhibits cell growth by altering the mitotic process [J].
Bruzzoni-Giovanelli, H ;
Faille, A ;
Linares-Cruz, G ;
Nemani, M ;
Le Deist, F ;
Germani, A ;
Chassoux, D ;
Millot, G ;
Roperch, JP ;
Amson, R ;
Telerman, A ;
Calvo, F .
ONCOGENE, 1999, 18 (50) :7101-7109
[4]   7 IN ABSENTIA, A GENE REQUIRED FOR SPECIFICATION OF R7 CELL FATE IN THE DROSOPHILA EYE [J].
CARTHEW, RW ;
RUBIN, GM .
CELL, 1990, 63 (03) :561-577
[5]  
DELLA NG, 1993, DEVELOPMENT, V117, P1333
[6]   The ubiquitin ligase component Siah1a is required for completion of meiosis I in male mice [J].
Dickins, RA ;
Frew, IJ ;
House, CM ;
O'Bryan, MK ;
Holloway, AJ ;
Haviv, I ;
Traficante, N ;
de Kretser, DM ;
Bowtell, DDL .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (07) :2294-2303
[7]   DEFINITION OF A CONSENSUS BINDING-SITE FOR P53 [J].
ELDEIRY, WS ;
KERN, SE ;
PIETENPOL, JA ;
KINZLER, KW ;
VOGELSTEIN, B .
NATURE GENETICS, 1992, 1 (01) :45-49
[8]   WAF1, A POTENTIAL MEDIATOR OF P53 TUMOR SUPPRESSION [J].
ELDEIRY, WS ;
TOKINO, T ;
VELCULESCU, VE ;
LEVY, DB ;
PARSONS, R ;
TRENT, JM ;
LIN, D ;
MERCER, WE ;
KINZLER, KW ;
VOGELSTEIN, B .
CELL, 1993, 75 (04) :817-825
[9]   Normal p53 function in primary cells deficient for Siah genes [J].
Frew, IJ ;
Dickins, RA ;
Cuddihy, AR ;
Del Rosario, M ;
Reinhard, C ;
O'Connell, MJ ;
Bowtell, DDL .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (23) :8155-8164
[10]   A TRANSCRIPTIONALLY ACTIVE DNA-BINDING SITE FOR HUMAN P53 PROTEIN COMPLEXES [J].
FUNK, WD ;
PAK, DT ;
KARAS, RH ;
WRIGHT, WE ;
SHAY, JW .
MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (06) :2866-2871