PROTEIN INTERACTIONS AND REPRESSION FUNCTION OF E1A

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DESCRIPTION: The E1A-associated protein, p300, is of major interest to cancer biologists because, as a direct target of the transforming functions of the adenovirus E1A gene, it is implicated in the regulation of both cell cycle specific and tissue specific gene expression. p300 is highly homologous to the CREB coactivator, CBP. CREB and CBP are the major mediators of the transcriptional response to cyclic AMP-responsive pathways. The relationship between p300 and CBP suggests that they perform, similar functions. Nevertheless, they are encoded by different genes, and preliminary clinical evidence indicates that specific metabolic disorders are linked with selective loss of CBP, indicating that p300 and CBP are not functionally redundant. The investigators identified a new 270 kilodalton product that is related to both p300 and CBP. p270 is particularly interesting because it exists in cells as a component of a tightly associated series of proteins. Moreover they have identified a prominent member of this complex as BRG1. The BRG1 protein product is a transcriptional activator, a regulator of gene expression pathways linked with the development and differentiation, and a putative DNA helicase. The p207/BRG1 complexes with this activity intact. The identification of this interaction should open the way to understanding a major part of the molecular mechanisms of action of the p300 and BRG1 families, two families of proteins that appear to be pivotal regulators of gene expression in pathways controlling cell proliferation and differentiation.