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PMID: 12389032 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Direct coupling of the cell cycle and cell death machinery by E2F.

Nature cell biology ·Vol. 4 ·No. 11 ·2002-11-00 ·Pages 859-64

Nahle Z, Polakoff J, Davuluri RV, McCurrach ME, Jacobson MD, Narita M, Zhang MQ, Lazebnik Y, Bar-Sagi D, Lowe SW

Abstract

Unrestrained E2F activity forces S phase entry and promotes apoptosis through p53-dependent and -independent mechanisms. Here, we show that deregulation of E2F by adenovirus E1A, loss of Rb or enforced E2F-1 expression results in the accumulation of caspase proenzymes through a direct transcriptional mechanism. Increased caspase levels seem to potentiate cell death in the presence of p53-generated signals that trigger caspase activation. Our results demonstrate that mitogenic oncogenes engage a tumour suppressor network that functions at multiple levels to efficiently induce cell death. The data also underscore how cell cycle progression can be coupled to the apoptotic machinery.

MeSH Terms

Adenovirus E1A Proteins/metabolism Animals Apoptosis Blotting, Northern Caspases/genetics,metabolism Cell Cycle Cell Cycle Proteins Cell Line, Tumor CpG Islands Cytochromes c/metabolism DNA-Binding Proteins E2F Transcription Factors E2F1 Transcription Factor Fibroblasts/metabolism Humans Luciferases/metabolism Mice Models, Biological Models, Genetic Promoter Regions, Genetic RNA/chemistry Retinoblastoma Protein/metabolism Time Factors Transcription Factors/chemistry,physiology Transcription, Genetic Tumor Suppressor Protein p53/metabolism

Chemicals

Adenovirus E1A Proteins Cell Cycle Proteins DNA-Binding Proteins E2F Transcription Factors E2F1 Transcription Factor E2F1 protein, human E2f1 protein, mouse Retinoblastoma Protein Transcription Factors Tumor Suppressor Protein p53 RNA Cytochromes c Luciferases Caspases

Authors & Affiliations

10 authors, click to expand affiliations / ORCID

Nahle Zaher

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

Polakoff Julia

Davuluri Ramana V

McCurrach Mila E

Jacobson Matthew D

Narita Masashi

Zhang Michael Q

Lazebnik Yuri

Bar-Sagi Dafna

Lowe Scott W

Article Info

Journal

Nature cell biology

Abbr.

Nat Cell Biol

ISSN

1465-7392

DOI

10.1038/ncb868

Published

2002-11-00

Pages

859-64

Language

English

Region

England

NLM ID

100890575

Subset

Grants

NCI NIH HHS · P30 CA008748 · United States

NCI NIH HHS · CA13106 · United States

NHGRI NIH HHS · HG01696 · United States

External Links

PubMed source DOI: 10.1038/ncb868 View journal details

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