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This increase in PUMA levels induces apoptosis through mitochondrial dysfunction. p53, and with it PUMA, is activated due to DNA damage caused by a variety of genotoxic agents. Other agents that induce p53 dependent apoptosis are neurotoxins, [16] [17] proteasome inhibitors, [18] microtubule poisons, [19] and transcription inhibitors. [20]
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 p63 p73 family is a family of tumor suppressor genes. [1] [2] This gene family codes the proteins: p53; TP73L (also known as "p63") p73; They are sometimes considered part of a "p53 family." When overexpressed, these proteins are known to be involved in tumor pathogenesis. [3]
P53, a transcription factor, can bind two sites within the human TIGAR gene to activate expression. [9] [13] One site is found within the first intron, and binds p53 with high affinity. [9] [13] The second is found just prior to the first exon, binds p53 with low affinity, [9] [13] and is conserved between mice and humans. [9]
Mutated apoptosis pathways causing disease are plentiful and have a wide range from cancer, due to lack of apoptosome activity, Alzheimer's disease due to too much apoptosome activity, and many other neurodegenerative diseases such as Parkinson's disease and Huntington's disease. [18]
Apoptosis (from Ancient Greek: ἀπόπτωσις, romanized: apóptōsis, lit. 'falling off') is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. [1] Biochemical events lead to characteristic cell changes and death. [2]
Apoptosis-stimulating of p53 protein 2 (ASPP2) also known as Bcl2-binding protein (Bbp) and tumor suppressor p53-binding protein 2 (p53BP2) is a protein that in humans is encoded by the TP53BP2 gene. [ 5 ] [ 6 ] [ 7 ] Multiple transcript variants encoding different isoforms have been found for this gene.
The p53 protein is heavily regulated [28] and contains more than 18 different phosphorylation sites. Activation of p53 can lead to cell cycle arrest, which can be reversed under some circumstances, or apoptotic cell death. [29] This activity occurs only in situations wherein the cell is damaged or physiology is disturbed in normal healthy ...