How many isoforms does p53 have?
The human p53 gene expresses 12 distinct p53 protein isoforms.
How does p53 regulate the cell?
The TP53 gene provides instructions for making a protein called tumor protein p53 (or p53). This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing (proliferating) too fast or in an uncontrolled way.
What is the p53 gene responsible for?
A gene that makes a protein that is found inside the nucleus of cells and plays a key role in controlling cell division and cell death. Mutations (changes) in the p53 gene may cause cancer cells to grow and spread in the body.
What activates p53 and what in turn does p53 do?
The p53 gene has been mapped to chromosome 17. In the cell, p53 protein binds DNA, which in turn stimulates another gene to produce a protein called p21 that interacts with a cell division-stimulating protein (cdk2). When p21 is complexed with cdk2 the cell cannot pass through to the next stage of cell division.
How does p53 stop cell cycle?
P53 forms a homotetrameric transcription factor that is reported to directly regulate ~500 target genes, thereby controlling a broad range of cellular processes, including cell cycle arrest, cell senescence, DNA repair, metabolic adaptation and cell death.
How does p53 become activated?
The tumour suppressor protein p53 is stabilised and activated in response to ionising radiation. This is known to depend on the kinase ATM; recent results suggest ATM acts via the downstream kinase Chk2/hCds1, which stabilises p53 at least in part by direct phosphorylation of residue serine 20.
What genes does p53 regulate?
How many amino acids are in p53?
The human p53 protein consists of 393 amino acids and contains four major functional domains.
How does p53 get activated?
How does p53 activate apoptosis?
P53 induces apoptosis in nontransformed cells mostly by direct transcriptional activation of the pro-apoptotic BH3-only proteins PUMA and (to a lesser extent) NOXA. Combined loss of the p53 effectors of apoptosis (PUMA plus NOXA) and cell cycle arrest/cell senescence (p21) does not cause spontaneous tumour development.
What happens when p53 is upregulated?
Upon p53 induction and phosphorylation, Mdm2 and p21 expression, both of which are induced by p53-mediated transcriptional activation, were upregulated. Dephosphorylation of pRb can be induced by the upregulated p21 through inhibiting cyclin-dependent kinase activities.
Is p53 constitutively active?
Significantly, these mutant alleles probably provide levels of constitutively activated p53 (Tyner et al., 2002). It is conceivable that constitutive or highly frequent activation of p53, such as under chronic exposure to stress, could result in accelerated aging.
How many p53 proteins does the human p53 gene express?
We have recently reported that the human p53 gene expresses not only 1 but 12 different p53 proteins (isoforms) due to alternative splicing, alternative initiation of translation, and alternative promoter usage. p53 isoform proteins thus contain distinct protein domains.
What is the role of p53 isoforms in the p53 pathway?
Therefore, we consider that p53 isoforms play essential roles in modulating p53 biological activities and are essential to the coordination of the multiple molecular pathways involved. Figure 4. Extracellular and intracellular signals integrated by a single cell in response to a low dose of doxorubicin.
Is p53 a multi-subunit protein composed of p63/p73 isoforms?
Several studies have shown that p53 isoforms are abnormally expressed in a wide range of cancers, suggesting that they play a role in carcinogenesis. As a molecular mechanism, we propose that the transcription factor p53 is in fact a multi-subunit protein composed of posttranslationally modified p53/p63/p73 isoforms.
What is Delta n-p53 (Delta p53)?
Courtois S, Verhaegh G, North S, et al. Delta N-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53. Oncogene. 2002;21:6722-8 [ PubMed] [ Google Scholar] 34. Grover R, Ray PS, Das S. Polypyrimidine tract binding protein regulates IRES-mediated translation of p53 isoforms.