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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 ]
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.
The p53 protein is a transcription factor that, when activated as part of the cell's response to stress, regulates many downstream target genes, including BID. However, p53 also has a transcription-independent role in apoptosis. In particular, p53 interacts with Bax, promoting Bax activation and the insertion of Bax into the mitochondrial membrane.
[85] p53 prevents the cell from replicating by stopping the cell cycle at G1, or interphase, to give the cell time to repair; however, it will induce apoptosis if damage is extensive and repair efforts fail. [86] Any disruption to the regulation of the p53 or interferon genes will result in impaired apoptosis and the possible formation of tumors.
The phase of the cell cycle at which the blockage occurs primarily depends on the p53 protein. In cells containing the so-called "wild type" (non-mutated) p53, the cell cycle is halted in the interphase, while in cells with mutated p53, it is halted in the G 2 /M phase. [44] [50] Mechanism of action of arsenic trioxide. [51]
p53 can be activated in response to a wide variety of cellular stressors, both oncogenic and non-oncogenic. An important checkpoint in a complex pathway, activated p53 has been shown to bind DNA and transcriptionally regulate genes that can mediate a variety of cellular growth processes including DNA repair , growth arrest, cellular senescence ...
The encoded protein mediates p53 inhibition of cell growth by activating AMP-activated protein kinase, which results in the inhibition of the mammalian target of rapamycin protein. The encoded protein also plays a critical role in antioxidant defense by regenerating overoxidized peroxiredoxins, and the expression of this gene is a potential ...
P53 causes cells to enter apoptosis and disrupt further cell division therefore preventing that cell from becoming cancerous (16). In the majority of cancers it is the p53 pathway that has become mutated resulting in lack of ability to terminate dysfunctional cells.