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The combination of these two mechanisms leads to apoptosis via activation of PUMA, Noxa and other proapoptotic proteins, resulting in mitochondrial dysfunction. [ 53 ] Other approaches focus on inhibiting antiapoptotic Bcl-2 family members just as PUMA does, allowing cells to undergo apoptosis in response to cancerous activity.
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.
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 serves as a transcription factors for both bax, a proapoptotic protein as well as p21, a CDK inhibitor. CDK Inhibitors result in cell cycle arrest. Arresting the cell provides the cell time to repair the damage, and if the damage is irreparable, p53 recruits bax to trigger apoptosis. [92]
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 ...
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 ...
Activated p53 proteins result in the expression of many proteins that are important in cell cycle arrest, repair, and apoptosis. At the G1/S checkpoint, p53 acts to ensure that the cell is ready for DNA replication, while at the G2/M checkpoint p53 acts to ensure that the cells have properly duplicated their content before entering mitosis. [40]
Apoptosis regulator BAX, also known as bcl-2-like protein 4, is a protein that in humans is encoded by the BAX gene. [5] BAX is a member of the Bcl-2 gene family . BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities.