Expression of transcription factor E2F1 induces quiescent cells to enter S phase

Abstract

Several lines of evidence implicate the E2F transcription factor as an important component of cell proliferation control. First, E2F binding sites are found in the promoters of genes responsive to proliferation signals and the level of E2F binding activity increases at a time when many of these genes are activated. Second, the tumour suppressor protein Rb, as well as the related p107 protein, complexes with E2F, resulting in an inhibition of E2F transcriptional activity. Third, oncogenic products of the DNA tumour viruses can dissociate these E2F complexes. We provide here direct evidence that E2F is involved in cellular proliferation control. Specifically, we demonstrate that overexpression of the E2F1 complementary DNA can activate DNA synthesis in cells that would otherwise growth-arrest, with an efficiency that is similar to that achieved by the expression of the adenovirus E1A gene. Moreover, microinjection of the E2F1 cDNA into quiescent cells can induce S-phase entry, whereas two E2F1 mutants, which are unable to transactivate the DHFR and TK promoters, are unable to induce S phase. We conclude that the E2F transcription factor plays an important role in progression into S phase and that this probably coincides with its capacity to stimulate transcription.

Life and death decisions by E2F-1

“…28 Several lines of evidence suggest that E2F-1 has the potential to function at an oncogene, promoting the proliferation of cells beyond their normal constraints. 29 It is an important part of the circuitry that commits cells to progression through the G1 phase, after which the cell is committed to complete the rest of the cell cycle. As eluded to earlier, many genes that are regulated in a cell-specific manner have E2F-binding sites as their promoters, and in some cases E2F-1 has been demonstrated to induce their expression directly.…”

K-ras modulates the cell cycle via both positive and negative regulatory pathways

“…Since the E2F family of transcription factors play a pivotal role in progression through the G 1 phase of the cell cycle and entry into S phase (Johnson et al, 1993), it was of interest to determine whether activated K-ras mediates cell cycle acceleration through regulation of any or all of the E2F family of transcription factors, of which ®ve members have been identi®ed to date. Of these ®ve members, E2F-1, 2, and 3 preferentially bind to pRb while E2F-4 and E2F-5 preferentially bind the pRb-related proteins p107 and p130, respectively (Beijersbergen et al, 1994;Hijmans et al, 1995).…”

E2F1 controls germ cell apoptosis during the first wave of spermatogenesis

“…As a result E2F1 activates transcription of genes required for DNA synthesis. In fact, activation of ectopic E2F1 expression is sufficient to induce cell cycle progression in quiescent cells (Johnson et al ., 1993). …”