Does phosphorylation activate or deactivate p53?

November 1, 2019 Off By idswater

Does phosphorylation activate or deactivate p53?

Together, these biochemical and genetic studies show that phosphorylation can activate p53 function, although these studies do not necessarily explain what selection pressures have maintained the integrity of the Ser20 and Ser392 phospho-acceptor sites during evolution in the urochordate-chordate lineage.

Does p53 promote 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 does phosphorylation of p53 do?

Although phosphorylation of p53 does not appear to be essential for p53 function, several studies have suggested that phosphorylation of p53 plays an important role in regulating p53 activities such as stability and DNA binding.

How is p53 degraded?

p53 is usually kept inactive due to ubiquitination by a number of E3 ubiquitin ligases that target p53 for proteasomal degradation. The ubiquitously expressed proto-oncogene Mdm2 is the major E3 ubiquitin ligase involved in this process and is critical for regulating p53 homeostasis.

What happens if p53 Cannot detect DNA damage?

This altered p53 protein cannot regulate cell growth and division and is unable to trigger apoptosis in cells with mutated or damaged DNA. As a result, DNA damage can accumulate in cells. If such cells continue to divide in an uncontrolled way, they can lead to the formation of bladder cancer.

What happens when p53 is overexpressed?

Our research showed that was a significant inverse correlation between p53 overexpression and response to chemotherapy and a stronger association between high P53 overexpression (%) and a genetic mutation of p53 (p=0.0001). More than 50% overexpression indicated a strong probability of genetic mutation.

How does p53 recognize DNA damage?

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.

Is p53 stable on its own?

In addition to failing to elicit a tumor suppressor response, these mutant p53s are also unable to activate expression of Mdm2, and as a result the mutant p53 proteins are unusually stable and accumulate to high levels in the tumor cells (Kubbutat and Vousden, 1998).

What causes the activation of p53?

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 stop the cell cycle?

Activated p53 can halt cell division in both the G1 and G2 phases of the cell division cycle. G1 is the preparation phase of the cell before replication of its DNA and G2 prepares the cell for mitosis.