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p53 pathway: In a normal cell, p53 is inactivated by its negative regulator, mdm2. Upon DNA damage or other stresses, various pathways will lead to the dissociation of the p53 and mdm2 complex. Once activated, p53 will induce a cell cycle arrest to allow either repair and survival of the cell or apoptosis to discard the damaged cell.
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.
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.
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. [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 ...
Mdm2 has been identified as a p53 interacting protein that represses p53 transcriptional activity. Mdm2 achieves this repression by binding to and blocking the N-terminal trans-activation domain of p53. Mdm2 is a p53 responsive gene—that is, its transcription can be activated by p53.
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.
P53 diverged from p63/p73 with a gene duplication in the cartilaginous fish. [7] P63 and p73 differentiated from each other in bony fish. [ 7 ] In vertebrates, p53 began the role of protecting the somatic cells and acting as a tumor suppressor.
In the field of genetics, a suicide gene is a gene that will cause a cell to kill itself through the process of apoptosis (programmed cell death). Activation of a suicide gene can cause death through a variety of pathways, but one important cellular "switch" to induce apoptosis is the p53 protein.
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