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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 .
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 ]
Part of this pathway includes alpha-interferon and beta-interferon, which induce transcription of the p53 gene, resulting in the increase of p53 protein level and enhancement of cancer cell-apoptosis. [88] 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 ...
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.
The action of the TIGAR/HK2 complex only protects cells from apoptosis under low oxygen conditions. Under normal or glucose starved conditions, TIGAR mediated protection from apoptosis comes from its bis-phosphatase activity alone. [21] TIGAR cannot prevent apoptosis via death pathways that are independent from ROS and p53. [9]
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 ]
The expression of BID is upregulated by the tumor suppressor p53, and BID has been shown to be involved in p53-mediated apoptosis. [7] 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 ...
This suggests that down-regulation of survivin by p53 is important for p53-mediated apoptotic pathway to successfully result in apoptosis. It is known that a defining characteristic of most tumors is the over-expression of survivin and the complete loss of wild-type p53. [17]