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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.
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 ...
p21 activated kinases (PAKs) are members of a family of enzymes. [1] They serve as targets for the small GTP binding proteins CDC42 and Rac and have been implicated in a wide range of biological activities. Members include: PAK1, regulating cell motility and morphology [2] PAK2, possibly playing a role in apoptosis [3]
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 ]
P53, p63, and p73 have similar features in their gene structures and functions but have also diverged evolutionarily. The p53 family evolved from an ancestor gene in unicellular life. [ 4 ] The ancestor gene functioned in germ line DNA protection early invertebrates. [ 5 ]
p53 mutations can function as a dominant negative, meaning that a mutated p53 protein can prevent the function of the natural protein produced from the non-mutated allele. [9] Other tumor-suppressor genes that do not follow the two-hit rule are those that exhibit haploinsufficiency , including PTCH in medulloblastoma and NF1 in neurofibroma .
The p53 upregulated modulator of apoptosis (PUMA) also known as Bcl-2-binding component 3 (BBC3), is a pro-apoptotic protein, member of the Bcl-2 protein family. [5] [6] In humans, the Bcl-2-binding component 3 protein is encoded by the BBC3 gene. [5] [6] The expression of PUMA is regulated by the tumor suppressor p53.
Tumor suppressor p53-binding protein 1 also known as p53-binding protein 1 or 53BP1 is a protein that in humans is encoded by the TP53BP1 gene. [ 5 ] [ 6 ] [ 7 ] Clinical significance
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