How is p53 activated?

How is p53 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.

Does p53 activate caspase?

Caspase activation by p53 occurs through the release of apoptogenic factors from the mitochondria, including cytochrome c and Smac/DIABLO.

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.

How does p53 gene work?

Normal Function 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.

Does p53 activate DNA repair?

Activation of p53 in response to DNA damage is associated with a rapid increase in its levels and with an increased ability of p53 to bind DNA and mediate transcriptional activation. This then leads to the activation of a number of genes whose products trigger cell-cycle arrest, apoptosis, or DNA repair.

What is the p53 pathway?

The p53 pathway is composed of a network of genes and their products that are targeted to respond to a variety of intrinsic and extrinsic stress signals that impact upon cellular homeostatic mechanisms that monitor DNA replication, chromosome segregation and cell division (Vogelstein et al., 2000).

Does the p53 protein repair DNA?

Already early in metazoan evolution, p53 started controlling the apoptotic demise of genomically compromised cells. p53 plays a prominent role as a facilitator of DNA repair by halting the cell cycle to allow time for the repair machineries to restore genome stability.

Is p53 pro or anti apoptotic?

Intriguingly, p53 was recently demonstrated to positively regulate expression of genes whose products are directly involved in both systems and owing to this, p53 clearly acts in an anti-apoptotic manner.

What type of gene is p53?

The p53 gene is a type of tumor suppressor gene. Also called TP53 gene and tumor protein p53 gene.

What causes p53 to be inactive at low levels normally?

Damage to p53-dependent mechanism is often caused by overexpression of MDM2, which codes for a p53-regulating protein. As a result, the level of active p53 is decreased and p53 induction in response to stress is weakened.

How does MDM2 regulate p53?

MDM2 negatively regulates p53 by targeting the ubiquitin ligase activity of MDM2. A complementary approach to prevent p53 degradation by MDM2 is to develop agents designed to inhibit the E3 ligase activity of MDM2 directly so as to mimic the effects of ARF or the ribosomal protein L11.

Is p53 negative good or bad?

In our clinical analysis, a negative (normal) p53 status proved to be associated with resistance to paclitaxel, whereas response was supported by deficient p53. Functional p53 has been found to arrest cell cycle in G1 phase to prevent transition into subsequent phases in the presence of DNA damage (26) .