Loss of dE2F Compromises Mitochondrial Function

被引：28

作者：

Ambrus, Aaron M. ^{[1
]}

Islam, Abul B. M. M. K. ^{[2
,3
]}

Holmes, Katherine B. ^{[1
]}

Moon, Nam Sung ^{[4
]}

Lopez-Bigas, Nuria ^{[2
,5
]}

Benevolenskaya, Elizaveta V. ^{[1
]}

Frolov, Maxim V. ^{[1
]}

机构：

[1] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA

[2] Univ Pompeu Fabra, Res Unit Biomed Informat, Dept Expt & Hlth Sci, Barcelona 08003, Spain

[3] Univ Dhaka, Dept Genet Engn & Biotechnol, Dhaka 1000, Bangladesh

[4] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada

[5] ICREA, Barcelona 08010, Spain

来源：

DEVELOPMENTAL CELL | 2013年 / 27卷 / 04期

基金：

美国国家卫生研究院;

关键词：

CELL-DEATH; TRANSCRIPTIONAL PROGRAM; S PHASE; APOPTOSIS; EXPRESSION; GENES; RB; PROLIFERATION; PROGRESSION; REPRESSION;

D O I：

10.1016/j.devcel.2013.10.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

E2F/DP transcription factors regulate cell proliferation and apoptosis. Here, we investigated the mechanism of the resistance of Drosophila dDP mutants to irradiation-induced apoptosis. Contrary to the prevailing view, this is not due to an inability to induce the apoptotic transcriptional program, because we show that this program is induced; rather, this is due to a mitochondrial dysfunction of dDP mutants. We attribute this defect to E2F/DP-dependent control of expression of mitochondria-associated genes. Genetic attenuation of several of these E2F/DP targets mimics the dDP mutant mitochondrial phenotype and protects against irradiation-induced apoptosis. Significantly, the role of E2F/DP in the regulation of mitochondrial function is conserved between flies and humans. Thus, our results uncover a role of E2F/DP in the regulation of mitochondrial function and demonstrate that this aspect of E2F regulation is critical for the normal induction of apoptosis in response to irradiation.

引用

页码：438 / 451

页数：14

共 44 条

[31] Cooperation between dE2F1 and Yki/Sd defines a distinct transcriptional program necessary to bypass cell cycle exit [J].

Nicolay, Brandon N. ;

Bayarmagnai, Battuya ;

Islam, Abul B. M. M. K. ;

Lopez-Bigas, Nuria ;

Frolov, Maxim V. .

GENES & DEVELOPMENT, 2011, 25 (04) :323-335

[32] Differential regulation of E2F1 apoptotic target genes in response to DNA damage [J].

Pediconi, N ;

Ianari, A ;

Costanzo, A ;

Belloni, L ;

Gallo, R ;

Cimino, L ;

Porcellini, A ;

Screpanti, I ;

Balsano, C ;

Alesse, E ;

Gulino, A ;

Levrero, M .

NATURE CELL BIOLOGY, 2003, 5 (06) :552-558

[33] Gitools: Analysis and Visualisation of Genomic Data Using Interactive Heat-Maps [J].

Perez-Llamas, Christian ;

Lopez-Bigas, Nuria .

PLOS ONE, 2011, 6 (05)

[34] p53 and E2f: partners in life and death [J].

Polager, Shirley ;

Ginsberg, Doron .

NATURE REVIEWS CANCER, 2009, 9 (10) :738-748

[35] Mutations in Drosophila DP and E2F distinguish G(1)-S progression from an associated transcriptional program [J].

Royzman, I ;

Whittaker, AJ ;

OrrWeaver, TL .

GENES & DEVELOPMENT, 1997, 11 (15) :1999-2011

[36] Drosophila IAP antagonists form multimeric complexes to promote cell death [J].

Sandu, Cristinel ;

Ryoo, Hyung Don ;

Steller, Hermann .

JOURNAL OF CELL BIOLOGY, 2010, 190 (06) :1039-1052

[37] Rb intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis [J].

Sankaran, Vijay G. ;

Orkin, Stuart H. ;

Walkley, Carl R. .

GENES & DEVELOPMENT, 2008, 22 (04) :463-475

[38] Regulation of apoptosis in Drosophila [J].

Steller, H. .

CELL DEATH AND DIFFERENTIATION, 2008, 15 (07) :1132-1138

[39] Regulation of apoptosis of rbf mutant cells during Drosophila development [J].

Tanaka-Matakatsu, Miho ;

Xu, Jinhua ;

Cheng, Leping ;

Du, Wei .

DEVELOPMENTAL BIOLOGY, 2009, 326 (02) :347-356

[40] mir-11 limits the proapoptotic function of its host gene, dE2f1 [J].

Truscott, Mary ;

Islam, Abul B. M. M. K. ;

Lopez-Bigas, Nuria ;

Frolov, Maxim V. .

GENES & DEVELOPMENT, 2011, 25 (17) :1820-1834

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