TY - JOUR
T1 - Expression of transcription factor E2F1 induces quiescent cells to enter S phase
AU - Johnson, David G.
AU - Schwarz, James K.
AU - Cress, W. Douglas
AU - Nevins, Joseph R.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1993
Y1 - 1993
N2 - 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 activated1-3. Second, the tumour suppressor protein Rb, as well as the related p107 protein, complexes with E2F2-7, resulting in an inhibition of E2F transcriptional activity3,8-12. Third, oncogenic products of the DNA tumour viruses can dissociate these E2F complexes 4,13. We provide here direct evidence that E2F is involved in cellular proliferation control. Specifically, we demonstrate that overexpression of the E2F1 complementary DNA14,15 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 El A 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.
AB - 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 activated1-3. Second, the tumour suppressor protein Rb, as well as the related p107 protein, complexes with E2F2-7, resulting in an inhibition of E2F transcriptional activity3,8-12. Third, oncogenic products of the DNA tumour viruses can dissociate these E2F complexes 4,13. We provide here direct evidence that E2F is involved in cellular proliferation control. Specifically, we demonstrate that overexpression of the E2F1 complementary DNA14,15 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 El A 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.
UR - http://www.scopus.com/inward/record.url?scp=0027491775&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027491775&partnerID=8YFLogxK
U2 - 10.1038/365349a0
DO - 10.1038/365349a0
M3 - Article
C2 - 8377827
AN - SCOPUS:0027491775
SN - 0028-0836
VL - 365
SP - 349
EP - 352
JO - Nature
JF - Nature
IS - 6444
ER -