Home LiteratureArticle Details
PMID: 11230146 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos.

Genes & development ·Vol. 15 ·No. 4 ·2001-02-15 ·Pages 386-91

Ziebold U, Reza T, Caron A, Lees JA

Abstract

The E2F transcription factors are thought to be key downstream targets of the retinoblastoma protein (pRB) tumor suppressor. It is widely believed that E2F1, E2F2, and E2F3 can all activate cellular proliferation but that E2F1 is the specific inducer of apoptosis. Here we show that the E2f3 mutation completely suppresses both the inappropriate proliferation and the p53-dependent apoptosis arising in the Rb mutant embryos. Through the analysis of Rb(-/-);E2f3(+/-) embryos, we have been able to separate E2F3's role in the induction of apoptosis from its ability to induce proliferation. Thus, contrary to the prevailing view of E2F action, E2F3 makes a major contribution to the apoptosis resulting from pRB loss.

MeSH Terms
Animals Apoptosis/genetics,physiology Cell Division/genetics,physiology E2F3 Transcription Factor Embryo, Mammalian/cytology Female Genes, Retinoblastoma Male Mice Mice, Inbred C57BL Mutation Pregnancy Transcription Factors/physiology
Chemicals
E2F3 Transcription Factor E2f3 protein, mouse Transcription Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ziebold U
Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Reza T
Caron A
Lees J A
References (22)
22 references, click to expand
  1. E2f3 is critical for normal cellular proliferation.
    Genes Dev. 2000 Mar 15;14(6):690-703 PMID: 10733529
  2. CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase.
    Mol Cell Biol. 1999 Sep;19(9):6379-95 PMID: 10454584
  3. A common E2F-1 and p73 pathway mediates cell death induced by TCR activation.
    Nature. 2000 Oct 5;407(6804):642-5 PMID: 11034214
  4. Role for the p53 homologue p73 in E2F-1-induced apoptosis.
    Nature. 2000 Oct 5;407(6804):645-8 PMID: 11034215
  5. Surfing the p53 network.
    Nature. 2000 Nov 16;408(6810):307-10 PMID: 11099028
  6. The retinoblastoma gene and gene product.
    Cancer Surv. 1992;12:43-57 PMID: 1638547
  7. Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis.
    Nature. 1992 Sep 24;359(6393):288-94 PMID: 1406932
  8. Effects of an Rb mutation in the mouse.
    Nature. 1992 Sep 24;359(6393):295-300 PMID: 1406933
  9. Requirement for a functional Rb-1 gene in murine development.
    Nature. 1992 Sep 24;359(6393):328-30 PMID: 1406937
  10. Heterozygous Rb-1 delta 20/+mice are predisposed to tumors of the pituitary gland with a nearly complete penetrance.
    Oncogene. 1994 Apr;9(4):1021-7 PMID: 8134105
  11. p53-dependent apoptosis produced by Rb-deficiency in the developing mouse lens.
    Nature. 1994 Sep 1;371(6492):72-4 PMID: 8072529
  12. Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis.
    Mol Cell Biol. 1994 Dec;14(12):8166-73 PMID: 7969153
  13. Deregulated expression of E2F family members induces S-phase entry and overcomes p16INK4A-mediated growth suppression.
    Mol Cell Biol. 1996 Mar;16(3):1047-57 PMID: 8622649
  14. E2F-4 switches from p130 to p107 and pRB in response to cell cycle reentry.
    Mol Cell Biol. 1996 Apr;16(4):1436-49 PMID: 8657117
  15. Mechanisms of carcinogenesis and the mutant mouse.
    Curr Opin Genet Dev. 1996 Feb;6(1):65-70 PMID: 8791481
  16. Loss of Rb activates both p53-dependent and independent cell death pathways in the developing mouse nervous system.
    EMBO J. 1996 Nov 15;15(22):6178-88 PMID: 8947040
  17. Distinct roles for E2F proteins in cell growth control and apoptosis.
    Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7245-50 PMID: 9207076
  18. The regulation of E2F by pRB-family proteins.
    Genes Dev. 1998 Aug 1;12(15):2245-62 PMID: 9694791
  19. Key roles for E2F1 in signaling p53-dependent apoptosis and in cell division within developing tumors.
    Mol Cell. 1998 Sep;2(3):283-92 PMID: 9774967
  20. Mutation of E2f-1 suppresses apoptosis and inappropriate S phase entry and extends survival of Rb-deficient mouse embryos.
    Mol Cell. 1998 Sep;2(3):293-304 PMID: 9774968
  21. The E2F-family proteins induce distinct cell cycle regulatory factors in p16-arrested, U343 astrocytoma cells.
    Oncogene. 1998 Aug 20;17(7):867-76 PMID: 9780003
  22. Id2 is a retinoblastoma protein target and mediates signalling by Myc oncoproteins.
    Nature. 2000 Oct 5;407(6804):592-8 PMID: 11034201
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.858801
Published
2001-02-15
Pages
386-91
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC312633
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.858801 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2