Abstract
The control of cell cycle progression is orchestrated by an extraordinary diverse and dynamic in function group of proteins. Critical in the progression are the actions of the E2F family of transcription factors which regulate the expression of genes necessary for the G1/S transition and the WAF/CIP/KIP family of cdk inhibitors which can inhibit cell cycle progression. In this report, we have identified E2F binding sites in both the human and mouse p21 promoters that bind E2F protein complexes from nuclear extracts in a cell cycle-dependent manner. In ectopic expression experiments we determined that E2F1, but not E2F4, can strongly transactivate the human p21 gene through these E2F binding sites which are located in the −215/+1 region of the p21 gene. The transactivation of the p21 gene through regulatory elements within the −215/+1 region of the promoter was correlated with increased levels of endogenous E2F1 and p21 proteins at the G1/S boundary. The significance of transactivation of the p21 gene by E2F is that p21 function is important in cell cycle progression as well as for cell cycle arrest. Indeed, E2F- induced levels of p21 protein during the G1/S transition is consistent with the recent findings demonstrating that p21 acts as an assembly factor for kinase active cyclin/cdk/p21 complexes.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hiyama, H., Iavarone, A. & Reeves, S. Regulation of the cdk inhibitor p21 gene during cell cycle progression is under the control of the transcription factor E2F. Oncogene 16, 1513–1523 (1998). https://doi.org/10.1038/sj.onc.1201667
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201667
Keywords
This article is cited by
-
Motif co-regulation and co-operativity are common mechanisms in transcriptional, post-transcriptional and post-translational regulation
Cell Communication and Signaling (2015)
-
The RB family is required for the self-renewal and survival of human embryonic stem cells
Nature Communications (2012)
-
p21 in cancer: intricate networks and multiple activities
Nature Reviews Cancer (2009)
-
The molecular programme of tumour reversion: the steps beyond malignant transformation
Nature Reviews Cancer (2009)
-
E2F1 mediates DNA damage and apoptosis through HCF-1 and the MLL family of histone methyltransferases
The EMBO Journal (2009)