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

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...

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Main Authors: Hsieh, J, Yap, D, O'Connor, D, Fogal, V, Fallis, L, Chan, F, Zhong, S, Lu, X
Format: Journal article
Language:English
Published: 2002
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author Hsieh, J
Yap, D
O'Connor, D
Fogal, V
Fallis, L
Chan, F
Zhong, S
Lu, X
author_facet Hsieh, J
Yap, D
O'Connor, D
Fogal, V
Fallis, L
Chan, F
Zhong, S
Lu, X
author_sort Hsieh, J
collection OXFORD
description 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.
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spelling oxford-uuid:260a5b1f-cd87-47bd-b8d8-24a95e83ed332022-03-26T11:58:52ZNovel function of the cyclin A binding site of E2F in regulating p53-induced apoptosis in response to DNA damage.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:260a5b1f-cd87-47bd-b8d8-24a95e83ed33EnglishSymplectic Elements at Oxford2002Hsieh, JYap, DO'Connor, DFogal, VFallis, LChan, FZhong, SLu, XWe 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.
spellingShingle Hsieh, J
Yap, D
O'Connor, D
Fogal, V
Fallis, L
Chan, F
Zhong, S
Lu, X
Novel function of the cyclin A binding site of E2F in regulating p53-induced apoptosis in response to DNA damage.
title Novel function of the cyclin A binding site of E2F in regulating p53-induced apoptosis in response to DNA damage.
title_full Novel function of the cyclin A binding site of E2F in regulating p53-induced apoptosis in response to DNA damage.
title_fullStr Novel function of the cyclin A binding site of E2F in regulating p53-induced apoptosis in response to DNA damage.
title_full_unstemmed Novel function of the cyclin A binding site of E2F in regulating p53-induced apoptosis in response to DNA damage.
title_short Novel function of the cyclin A binding site of E2F in regulating p53-induced apoptosis in response to DNA damage.
title_sort novel function of the cyclin a binding site of e2f in regulating p53 induced apoptosis in response to dna damage
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