Mar 31, 2022 · Following activation of p53, for example by viral infection or induction of DNA damage, p21 expression is upregulated. High levels of p21 then result in RB-E2F complex formation and...

May 20, 2004 · We confirmed direct interaction of E2F-1 with the proximal region of the p21 promoter. Interestingly, elevated E2F-1 activity was sufficient to arrest a substantial subset of cells in S phase and this effect was correlated to and dependent on the induction of p21 protein.

p21 inhibits cell cycle progression primarily through the inhibition of CDK2 activity, which is required not only for the phosphorylation of RB with the consequent release and activation of E2f-dependent gene expression, but also for the firing of replication origins and for the activity of proteins directly involved in DNA synthesis 17.

Mar 29, 2004 · Here, we show that constitutive expression of E2F-1 induces endogenous p21 expression and that p21 is responsible for E2F-1-dependent S phase cell cycle arrest.

Jun 1, 2016 · P21 is a well-known inhibitor of cell cycle and can arrest the cell cycle progression in G1/S and G2/M transitions by inhibiting CDK4,6/cyclin-D and CDK2/cyclin-E, respectively. It is believed that the regulation of cell growth by p21 is mediated by control of E2F activity [3], [4].

Following activation of p53, for example by viral infection or induction of DNA damage, p21 expression is upregulated. High levels of p21 then result in RB-E2F complex formation and downregulation of a large number of cell cycle genes. Thus, p53-dependent transcriptional repression is indirect.

Using a conditional gene-targeting approach, we show that the targeted disruption of the entire E2F activator subclass composed of E2f1, E2f2, and E2f3 in mouse embryonic fibroblasts leads to the activation of p53 and the induction of p53 target genes, including p21CIP1.

In addition to its inhibition of CDK enzymes and proliferating cell nuclear antigen function in DNA replication, these studies reveal a novel mechanism by which p21 mediates growth arrest: direct interaction with E2F complexes and negative regulation of E2F transcription factor activity.

Following activation of p53, for example by viral infection or induction of DNA damage, p21 expression is upregulated. High levels of p21 then result in RB-E2F complex formation and downregulation of a large number of cell cycle genes. Thus, p53-dependent transcriptional repression is indirect.

Several observations suggest that the induction of p21 CIP1 in E2f1-3-deficient cells is likely an important p53-regulated event contributing to the inhibition of E2F target gene expression and the block at G 1 /S.