E2F-3B is a physiological target of cyclin A.
The E2F family of transcription factors controls the expression of numerous genes that are required for the G(1)/S transition. Among the mechanisms that modulate the activity of the E2F proteins, cyclin A has been found to be important for the down-regulation of E2F-1, -2, and -3A activity after cells have progressed through G(1)/S. Specifically, phosphorylation of these E2F proteins by cyclin A/Cdk2 ultimately results in their necessary degradation as cells progress through S phase. E2F-3B was recently identified as an alternatively spliced form of E2F-3A that was predicted to lack a functional cyclin A binding domain. In this paper, we present considerable evidence that contradicts this prediction. First, we demonstrate binding of cyclin A to E2F-3B as bacterially expressed proteins in vitro. Second, we demonstrate binding of cyclin A to E2F-3B in mammalian cells in vivo. Third, we show that co-expression of cyclin A with E2F-3B significantly reduces E2F-3B-mediated transcriptional activity. Finally, in synchronized cells, we observe down-regulation of E2F-3B protein expression coincident with the up-regulation of cyclin A. We conclude that E2F-3B is a physiological target of cyclin A.
He
Yiwen
Y
Department of Biochemistry and Molecular Biology, University of South Florida, College of Medicine, Tampa 33612, USA.
Cress
W Douglas
WD
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle; D019925:Cyclin A / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D050699:E2F3 Transcription Factor; D051379:Mice; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology
D019925:Cyclin A; D050699:E2F3 Transcription Factor; C490840:E2f3 protein, mouse; D014157:Transcription Factors; D004247:DNA