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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 ]
[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.
PUMA can also function as an indicator of p53 mutations. Many cancers exhibit mutations in the p53 gene, but this mutation can only be detected through extensive DNA sequencing. Studies have shown that cells with p53 mutations have significantly lower levels of PUMA, making it a good candidate for a protein marker of p53 mutations, providing a ...
TIGAR is a fructose bisphosphatase which activates p53, in results of inhibiting the expression of glucose transporter and also regulating the expression of hexokinase and phosphoglycerate mutase. TIGAR also inhibit the Phosphofructokinase (PFK) by lowering the level of fructose-2,6,bisphosphate, therefore, glycolysis is inhibited and pentose ...
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 function can also be responsible for a limited life span where mutations of the p53 gene causes expression of dominant-negative forms producing long lived animals. For example in an experiment using C. elegans , the increased life span of p53 mutants was found to depend on increased autophagy. [ 19 ]
The tumor suppressor gene p53 regulates DNA repair and can induce apoptosis in dysregulated cells. E Soto-Reyes and F Recillas-Targa elucidated the importance of the CTCF protein in regulating p53 expression. [28] CTCF, or CCCTC binding factor, is a zinc finger protein that insulates the p53 promoter from accumulating repressive histone marks ...
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 ...