Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development

被引：177

作者：

Li, Jing ^{[1
,2
]}

Ran, Cong ^{[1
,2
]}

Li, Edward ^{[1
,2
]}

Gordon, Faye ^{[1
,2
]}

Comstock, Grant ^{[1
,2
]}

Siddiqui, Hasan ^{[1
,2
]}

Cleghorn, Whitney ^{[1
,2
]}

Chen, Hui-Zi ^{[1
,2
]}

Kornacker, Karl ^{[3
]}

Liu, Chang-Gong ^{[1
]}

Pandit, Shusil K. ^{[4
]}

Khanizadeh, Mehrbod ^{[4
]}

Weinstein, Michael ^{[1
,2
]}

Leone, Gustavo ^{[1
,2
]}

de Bruin, Alain ^{[1
,2
]}

机构：

[1] Ohio State Univ, Human Canc Genet Program, Dept Mol Virol Immunol & Med Genet, Ctr Comprehens Canc, Columbus, OH 43210 USA

[2] Ohio State Univ, Coll Biol Sci, Dept Mol Genet, Columbus, OH 43210 USA

[3] Ohio State Univ, Div Sensory Biophys, Columbus, OH 43210 USA

[4] Univ Utrecht, Fac Vet Med, Dept Pathobiol, NL-3584 CL Utrecht, Netherlands

来源：

DEVELOPMENTAL CELL | 2008年 / 14卷 / 01期

关键词：

D O I：

10.1016/j.devcel.2007.10.017

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The E2f7 and E2f8 family members are thought to function as transcriptional repressors important for the control of cell proliferation. Here, we have analyzed the consequences of inactivating E2f7 and EM in mice and show that their individual loss had no significant effect on development. Their combined ablation, however, resulted in massive apoptosis and dilation of blood vessels, culminating in lethality by embryonic day E11.5. A deficiency in E2f7 and E2f8 led to an increase in E2f1 and p53, as well as in many stress-related genes. Homo- and heterodimers of E2F7 and E2F8 were found on target promoters, including E2f1. Importantly, loss of either E2f1 or p53 suppressed the massive apoptosis in double-mutant embryos. These results identify E2F7 and E2F8 as a unique repressive arm of the E2F transcriptional network that is critical for embryonic development and control of the E2F1-p53 apoptotic axis.

引用

页码：62 / 75

页数：14

共 44 条

[1] Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter [J].

Araki, K ;

Nakajima, Y ;

Eto, K ;

Ikeda, MA .

ONCOGENE, 2003, 22 (48) :7632-7641

[2] The E2F family: specific functions and overlapping interests [J].

Attwooll, C ;

Denchi, EL ;

Helin, K .

EMBO JOURNAL, 2004, 23 (24) :4709-4716

[3] E2F target genes: unraveling the biology [J].

Bracken, AP ;

Ciro, M ;

Cocito, A ;

Helin, K .

TRENDS IN BIOCHEMICAL SCIENCES, 2004, 29 (08) :409-417

[4] Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription [J].

Christensen, J ;

Cloos, P ;

Toftegaard, U ;

Klinkenberg, D ;

Bracken, AP ;

Trinh, E ;

Heeran, M ;

Di Stefano, L ;

Helin, K .

NUCLEIC ACIDS RESEARCH, 2005, 33 (17) :5458-5470

[5] Identification and characterization of E2F7, a novel mammalian E2F family member capable of blocking cellular proliferation [J].

de Bruin, A ;

Maiti, B ;

Jakoi, L ;

Timmers, C ;

Buerki, R ;

Leone, G .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (43) :42041-42049

[6] Distinct roles for E2F proteins in cell growth control and apoptosis [J].

DeGregori, J ;

Leone, G ;

Miron, A ;

Jakoi, L ;

Nevins, JR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (14) :7245-7250

[7]

DeGregori J, 2006, CURR MOL MED, V6, P739

[8] E2F7, a novel E2F featuring DP-independent repression of a subset of E2F-regulated genes [J].

Di Stefano, L ;

Jensen, MR ;

Helin, K .

EMBO JOURNAL, 2003, 22 (23) :6289-6298

[9] ACCURATE TRANSCRIPTION INITIATION BY RNA POLYMERASE-II IN A SOLUBLE EXTRACT FROM ISOLATED MAMMALIAN NUCLEI [J].

DIGNAM, JD ;

LEBOVITZ, RM ;

ROEDER, RG .

NUCLEIC ACIDS RESEARCH, 1983, 11 (05) :1475-1489

[10] The E2F transcriptional network: old acquaintances with new faces [J].

Dimova, DK ;

Dyson, NJ .

ONCOGENE, 2005, 24 (17) :2810-2826

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