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PMID: 11739724 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Novel function of the cyclin A binding site of E2F in regulating p53-induced apoptosis in response to DNA damage.

Molecular and cellular biology ·Vol. 22 ·No. 1 ·2002-01-00 ·Pages 78-93

Hsieh JK, Yap D, O'Connor DJ, Fogal V, Fallis L, Chan F, Zhong S, Lu X

Abstract

We demonstrate here that the E2F1 induced by DNA damage can bind to and promote the apoptotic function of p53 via the cyclin A binding site of E2F1. This function of E2F1 does not require its DP-1 binding, DNA binding, or transcriptional activity and is independent of mdm2. All the cyclin A binding E2F family members can interact and cooperate with p53 to induce apoptosis. This suggests a novel role for E2F in regulating apoptosis in response to DNA damage. Cyclin A, but not cyclin E, prevents E2F1 from interacting and cooperating with p53 to induce apoptosis. However, in response to DNA damage, cyclin A levels decrease, with a concomitant increase in E2F1-p53 complex formation. These results suggest that the binding of E2F1 to p53 can specifically stimulate the apoptotic function of p53 in response to DNA damage.

MeSH Terms
Apoptosis/physiology Binding Sites Cell Cycle Proteins Cell Separation Cyclin A/metabolism DNA Damage DNA-Binding Proteins/genetics,metabolism E2F Transcription Factors E2F1 Transcription Factor Flow Cytometry Humans Neoplasm Proteins/metabolism Nuclear Proteins Precipitin Tests Protein Binding Protein Structure, Tertiary Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-bcl-2 Proto-Oncogene Proteins c-mdm2 Transcription Factors/chemistry,genetics,metabolism Tumor Cells, Cultured Tumor Suppressor Protein p53/metabolism Ultraviolet Rays bcl-2-Associated X Protein
Chemicals
Cell Cycle Proteins Cyclin A DNA-Binding Proteins E2F Transcription Factors E2F1 Transcription Factor E2F1 protein, human Neoplasm Proteins Nuclear Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Transcription Factors Tumor Suppressor Protein p53 bcl-2-Associated X Protein MDM2 protein, human Proto-Oncogene Proteins c-mdm2
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Hsieh Jung-Kuang
Ludwig Institute for Cancer Research, Imperial College School of Medicine, London W2 1PG, United Kingdom.
Yap Damian
O'Connor Daniel J
Fogal Valentina
Fallis Lynn
Chan Florence
Zhong Shan
Lu Xin
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43 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.22.1.78-93.2002
Published
2002-01-00
Pages
78-93
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC134205
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.22.1.78-93.2002 PMC Full Text View journal details
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