In the presence of p53, p21 is induced and inhibits Cdk1, thereby contributing to prolong the G2/M arrest (Bunz et al., 1998). Activation of the DNA damage checkpoint and a transient cell cycle block in response to irradiation allows cells to induce DNA repair.

p21 is a potent cyclin-dependent kinase inhibitor (CKI). The p21 (CIP1/WAF1) protein binds to and inhibits the activity of cyclin-CDK2, -CDK1, and -CDK4 /6 complexes, and thus functions as a regulator of cell cycle progression at G 1 and S phase.

Mar 31, 2022 · Here, their functional interaction through the cyclin-dependent kinase inhibitor p21/CDKN1A is described. The resulting p53-p21-RB mechanism controls transcription of a large number...

This nuclear retention, which strictly depends on association with endogenous p21, prevents activation of cyclin B1-Cdk1 by Cdc25 and Cdk-activating kinase as well as its recruitment to the centrosome.

Cyclin B1-Cdk1 complexes are maintained in an inactive state by association with p21, which provokes nuclear retention of cyclin B1-Cdk1 and prevents their activation at the centrosome and, possibly, in the cytoplasm and nucleus.

CDK1, at least in some tissues, may be the crucial target of p21 in tumorigenesis 27 because p21 effectively inhibits the kinase activity of CDK1 both in unstressed cells and after genotoxic stresses, leading to growth arrest in the G2 phase of the cell cycle 21 – 26 .

Non-phosphorylatable p21 binds strongly to Cdk1/cyclin B1. To gain insight into the binding affinity of p21 and its mutants to Cdk1/cyclin B1, pulldown assays were performed using different GST-p21 recombinant proteins incubated with cellular extracts from mitotic HCT116 p21−/− cells.

Jun 1, 2016 · Cyclin-dependent kinase (CDK) inhibitor p21 (also known as p21 WAF1/Cip1) is one of these factors that promote cell cycle arrest in response to a variety of stimuli. The inhibitory effect of P21 on cell cycle progression correlates with its nuclear localization. P21 can be induced by both p53-dependent and p53-independent mechanisms.

Here we present evidence that this is possible due to premature translocation of Cdk1 from the cytoplasm to the nucleus in the absence of Cdk2. We also investigated the consequence of loss of Cdk2 on the maintenance of the G1/S DNA damage checkpoint.

Aug 2, 2016 · The multifunctional protein p21Cip1/CDKN1A (p21) is an important and universal Cdk-interacting protein. Recently, we have reported that p21 is involved in the regulation of the mitotic kinase Cdk1/cyclin B1 and critical for successful mitosis and cytokinesis.