The E2F transcription factors: key regulators of cell proliferation

Ever since its discovery, the RE-I gene and the corresponding protein, pRB, have been a focal point of cancer research. The isolation of E2F transcrip tion factors provided the key to our current understanding of RE-I function in the regulation of the cell cycle and in tumor suppression. It is becomi ng more and more evident that the regulatory circuits governing the cell cy cle are very complex and highly interlinked. Certain aspects of RB-1 functi on, for instance its role in differentiation, cannot be easily explained by the current models of pRB-E2F interaction. One reason is that pRB has targ ets different from E2F, molecules like MyoD for instance. Another reason ma y be that we have not completely understood the full complexity of E2F func tion, itself. In this review, we will try to illuminate the role of E2F in pRB- and p53-mediated tumor suppression pathways with particular emphasis o n the aspect of E2F-mediated transcriptional regulation. We conclude that E 2F can mediate transcriptional activation as well as transcriptional repres sion of E2F target genes. The net effect of E2F on the transcriptional acti vity of a particular gene may be the result of as yet poorly understood pro tein-protein interactions of E2F with other components of the transcription al machinery, as well as it may reflect the readout of the different ways o f regulating E2F activity, itself. We will discuss the relevance of a thoro ugh understanding of E2F function for cancer therapy. (C) 2000 Elsevier Sci ence B.V. All rights reserved.