Identification of an E1A-inducible cellular factor that interacts with regulatory sequences within the adenovirus E4 promoter.
AUTOR(ES)
Raychaudhuri, P
RESUMO
We have previously shown that E1A-mediated induction of the adenovirus E2 transcription unit likely involves the posttranslational activation of a previously limiting cellular factor termed E2F. However, this factor is not involved in E1A induction of several other viral genes, including the E4 gene, since it does not bind to the promoters of these genes. We have undertaken an analysis of proteins which bind to the E4 promoter in an attempt to define the basis for E1A control of this gene. Gel retardation binding assays revealed a large number of interactions with the E4 promoter consistent with the fact that at least 180 nucleotides of sequence are required for full promoter activity. The analysis was simplified by employing small probes as well as by using partially fractionated extracts. By so doing, we have identified at least seven discrete factor interactions involving the E4 promotor. Multiple interactions, as defined by discrete gel complexes, were identified with a site previously shown to be critical for promoter activity as well as E1A control. We find that one of these factors, termed E4F, is increased at least 10-fold in extracts prepared from Ad5 infected cells and that the increase requires the E1A gene. Furthermore, the activation is maximal by 3 h post-infection, consistent with the kinetics of activation of E4 transcription. Competition binding assays demonstrated that the E4F factor was E4 specific and did not interact with any other E1A inducible promoter. We therefore conclude that the induced E4F factor is likely responsible for the E1A-induced transcription of E4, thereby suggesting that E1A control must involve an activation of multiple promoter specific binding proteins.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=553890Documentos Relacionados
- A cellular transcription factor E4F1 interacts with an E1a-inducible enhancer and mediates constitutive enhancer function in vitro.
- Adenovirus 5 E2 transcription unit: an E1A-inducible promoter with an essential element that functions independently of position or orientation.
- A cellular protein, activating transcription factor, activates transcription of multiple E1A-inducible adenovirus early promoters.
- Adeno-associated virus P5 promoter contains an adenovirus E1A-inducible element and a binding site for the major late transcription factor.
- Adenovirus E4 open reading frame 4 protein autoregulates E4 transcription by inhibiting E1A transactivation of the E4 promoter.