E2F1 mediates DNA damage and apoptosis through HCF-1 and the MLL family of histone methyltransferases.

Détails

ID Serval
serval:BIB_23FC0FE74C64
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
E2F1 mediates DNA damage and apoptosis through HCF-1 and the MLL family of histone methyltransferases.
Périodique
EMBO Journal
Auteur(s)
Tyagi S., Herr W.
ISSN
1460-2075[electronic]
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
28
Numéro
20
Pages
3185-3195
Langue
anglais
Résumé
E2F1 is a key positive regulator of human cell proliferation and its activity is altered in essentially all human cancers. Deregulation of E2F1 leads to oncogenic DNA damage and anti-oncogenic apoptosis. The molecular mechanisms by which E2F1 mediates these two processes are poorly understood but are important for understanding cancer progression. During the G1-to-S phase transition, E2F1 associates through a short DHQY sequence with the cell-cycle regulator HCF-1 together with the mixed-lineage leukaemia (MLL) family of histone H3 lysine 4 (H3K4) methyltransferases. We show here that the DHQY HCF-1-binding sequence permits E2F1 to stimulate both DNA damage and apoptosis, and that HCF-1 and the MLL family of H3K4 methyltransferases have important functions in these processes. Thus, HCF-1 has a broader role in E2F1 function than appreciated earlier. Indeed, sequence changes in the E2F1 HCF-1-binding site can modulate both up and down the ability of E2F1 to induce apoptosis indicating that HCF-1 association with E2F1 is a regulator of E2F1-induced apoptosis.
Mots-clé
Apoptosis, DNA damage, E2F1, HCF-1, MLL, Oncogene-Induced Senescence, Cell-Cycle Progression, S-Phase, E2f1-Induced Apoptosis, Activation, P53, Proteins, Cancer, Gene, P21
Pubmed
Web of science
Open Access
Oui
Création de la notice
04/11/2009 11:05
Dernière modification de la notice
08/05/2019 15:49
Données d'usage