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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.
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often spoken of as, a single protein) are crucial in vertebrates , where they prevent cancer formation. [ 5 ]
Human cells contain many different cyclins that bind to different CDKs. CDKs and cyclins appear and activate at specific cell cycle phases. Seven cyclin-dependent kinase inhibitor proteins have been identified. They are p15, p16, p18, p19, p21, p27, and p57. [7]
Chk1/2 phosphorylate cdc25 which, in addition to being inhibited, is also sequestered in the cytoplasm by the 14-3-3 proteins. 14-3-3 are upregulated by p53, which, as previously mentioned, is activated by Chk1 and ATM/ATR. p53 also transactivates p21, and both p21 and the 14-3-3 in turn inhibit cyclin B-cdc2 complexes through the ...
P14ARF is a central actor of the cell cycle regulation process as it participates to the ARF-MDM2-p53 pathway and the Rb-E2F-1 pathway. [15] It is the physiological inhibitor of MDM2, an E3 ubiquitin ligase controlling the activity and stability of P53, and loss of P14ARF activity may have a similar effect as loss of P53. [16]
In the absence of p53 or p21, it was demonstrated that radiated cells progressed into mitosis. [17] The absence of p21 or 14-3-3 cannot sufficiently inhibit the CyclinB-Cdc2 complex, thus exhibiting the regulatory control of p53 and p21 in the G2 checkpoint in response to DNA damage. [12] p53 mutations can result in a significant checkpoint ...
19645 Ensembl ENSG00000139687 ENSMUSG00000022105 UniProt P06400 P13405 RefSeq (mRNA) NM_000321 NM_009029 RefSeq (protein) NP_000312 NP_000312.2 NP_033055 Location (UCSC) Chr 13: 48.3 – 48.6 Mb Chr 14: 73.42 – 73.56 Mb PubMed search Wikidata View/Edit Human View/Edit Mouse The retinoblastoma protein (protein name abbreviated Rb or pRb ; gene name abbreviated Rb, RB or RB1) is a tumor ...
Rb and p53 regulate the transition between G1 and S phase, arresting the cell cycle before DNA replication until the appropriate checkpoint inputs, such as DNA damage repair, are completed. [20] p53 regulates the p21 gene, which produces a protein which binds to the Cyclin D-Cdk4/6 complex. [21]