Pocket Protein-Independent Repression of Urokinase-Type Plasminogen Activator and Plasminogen Activator Inhibitor 1 Gene Expression by E2F1
AUTOR(ES)
Koziczak, Magdalena
FONTE
American Society for Microbiology
RESUMO
Expression of genes of the plasminogen activator (PA) system declines at the G0/G1-S-phase boundary of the cell cycle. We found that overexpression of E2F1-3, which acts mainly in late G1, inhibits promoter activity and endogenous expression of the urokinase-type PA (uPA) and PA inhibitor 1 (PAI-1) genes. This effect is dose dependent and conserved in evolution. Mutation analysis indicated that both the DNA-binding and transactivation domains of E2F1 are necessary for this regulation. Interestingly, an E2F1 mutant lacking the pRB-binding region strongly repressed the uPA and PAI-1 promoters. An E2F-mediated negative effect was also observed in pRB and p107/p130 knockout cell lines. This is the first report that E2F can act as a repressor independently of pocket proteins. Mutation of AP-1 elements in the uPA promoter abrogated E2F-mediated transcriptional inhibition, suggesting the involvement of AP-1 in this regulation. Results shown here identify E2F as an important component of transcriptional control of the PA system and thus provide new insights into mechanisms of cellular proliferation.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=110818Documentos Relacionados
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