Acetylation status of E2F-1 has an important role in the regulation of E2F-1-mediated transactivation of tumor suppressor p73

被引：17

作者：

Ozaki, Toshinori ^{[1
]}

Okoshi, Rintaro ^{[1
]}

Sang, Meixiang ^{[1
]}

Kubo, Natsumi ^{[1
]}

Nakagawara, Akira ^{[1
]}

机构：

[1] Chiba Canc Ctr, Res Inst, Div Biochem, Chiba 2608717, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 386卷 / 01期

基金：

日本学术振兴会;

关键词：

Acetylation; Adriamycin; Apoptosis; DNA damage; E2F-1; p73; UBIQUITIN-PROTEIN LIGASE; APOPTOTIC TARGET GENES; KINASE C-ABL; DNA-DAMAGE; P53; FAMILY; CELL-CYCLE; ACTIVATION; EXPRESSION; DEATH; REPLICATION;

D O I：

10.1016/j.bbrc.2009.06.035

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Tumor suppressor p73 plays an important role in the regulation of DNA damage response. E2F-1 acts as a transcriptional regulator for p73. In the present study, we have found that acetylation of E2F-1 has a critical role in the E2F-1-mediated transactivation of p73. In response to adriamycin (ADR), p73 was stabilized in HeLa cells and the expression levels of its target genes increased in association with an induction of apoptosis. Of note, E2F-1 and several its target genes were transactivated in response to ADR, whereas p73 mRNA level remained unchanged. Immunoprecipitation analysis revealed that ADR has a marginal effect on acetylation status of E2F-1. Intriguingly, acetylation level of E2F-1 remarkably increased in the presence of trichostatin A (TSA) and thereby inducing the expression level of p73 mRNA. Taken together, our present findings suggest that acetylation status of E2F-1 contributes to the selective activation of its target genes. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：207 / 211

页数：5

共 33 条

[1]

Agami R, 1999, NATURE, V399, P809

[2] p14ARF links the tumour suppressors RB and p53 [J].

Bates, S ;

Phillips, AC ;

Clark, PA ;

Stott, F ;

Peters, G ;

Ludwig, RL ;

Vousden, KH .

NATURE, 1998, 395 (6698) :124-125

[3] The E2F-1 transcription factor promotes caspase-8 and Bid expression, and enhances Fas signaling in T cells [J].

Cao, QY ;

Xia, Y ;

Azadniv, M ;

Crispe, IN .

JOURNAL OF IMMUNOLOGY, 2004, 173 (02) :1111-1117

[4] p73 is transcriptionally regulated by DNA damage, p53, and p73 [J].

Chen, XB ;

Zheng, YM ;

Zhu, JH ;

Jiang, JY ;

Wang, J .

ONCOGENE, 2001, 20 (06) :769-774

[5] DNA damage-dependent acetylation of p73 dictates the selective activation of apoptotic target genes [J].

Costanzo, A ;

Merlo, P ;

Pediconi, N ;

Fulco, M ;

Sartorelli, V ;

Cole, PA ;

Fontemaggi, G ;

Fanciulli, M ;

Schiltz, L ;

Blandino, G ;

Balsano, C ;

Levrero, M .

MOLECULAR CELL, 2002, 9 (01) :175-186

[6] Tumor predisposition in mice mutant for p63 and p73:: Evidence for broader tumor suppressor functions for the p53 family [J].

Flores, ER ;

Sengupta, S ;

Miller, JB ;

Newman, JJ ;

Bronson, R ;

Crowley, D ;

Yang, A ;

McKeon, F ;

Jacks, T .

CANCER CELL, 2005, 7 (04) :363-373

[7]

Gong JG, 1999, NATURE, V399, P806

[8] p53 family genes: structural comparison, expression and mutation [J].

Ikawa, S ;

Nakagawara, A ;

Ikawa, Y .

CELL DEATH AND DIFFERENTIATION, 1999, 6 (12) :1154-1161

[9] Role for the p53 homologue p73 in E2F-1-induced apoptosis [J].

Irwin, M ;

Marin, MC ;

Phillips, AC ;

Seelan, RS ;

Smith, DI ;

Liu, WG ;

Flores, ER ;

Tsai, KY ;

Jacks, T ;

Vousden, KH ;

Kaelin, WG .

NATURE, 2000, 407 (6804) :645-648

[10] Chemosensitivity linked to p73 function [J].

Irwin, MS ;

Kondo, K ;

Marin, MC ;

Cheng, LS ;

Hahn, WC ;

Kaelin, WG .

CANCER CELL, 2003, 3 (04) :403-410

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