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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 ]
p21 Cip1 (alternatively p21 Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, [5] though is primarily associated with inhibition of CDK2.
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]
[11] [12] These pathways also stimulate the tumor suppressor p53. p53 regulates the function of the Cdk2 inhibitor p21 and the 14-3-3 proteins that phosphorylate (and thereby inactivate) and sequester Cdc25 in the cytoplasm, respectively. [13] Recent studies have also suggested that Cdk1 and 14-3-3 positively regulate Wee1 in a similar manner.
In addition, another mechanism by which p21 is activated is through the accumulation of p16 in response to DNA damage. p16 disrupts cyclin D-CDK4 complexes, thus causing the release of p21 from the complexes, which leads to the dephosphorylation and activation of Rb, which allows Rb to bind and inhibit E2F 1–3, thus keeping the cell from ...
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 ...
Both of these pathways are activated in response to cellular stressors and lead to cell cycle inhibition. p53 activates p21 which deactivates cyclin-dependent kinase 2(Cdk 2). Without Cdk 2, retinoblastoma protein (pRB) remains in its active, hypophosphorylated form and binds to the transcription factor E2F1 , an important cell cycle regulator ...
At cell cycle level there is an increase of complexity of the mechanisms in somatic stem cells. However, it is observed a decrease of self-renewal potential with age. These mechanisms are regulated by p16 Ink4a-CDK4/6-Rb and p19 Arf-p53-P21 Cip1 signaling pathways. Embryonic stem cells have constitutive cyclin E-CDK2 activity, which ...