What type of regulator is p53?

The p53 protein is subject to tight regulation at multiple levels. This is achieved by a variety of positive and negative regulators, often creating feedback loops. Three major levels of regulation are recognized: protein stability, protein activity, and subcellular distribution.

What are two cell processes that are regulated by p53?

Cell-cycle arrest and apoptosis are the most prominent outcomes of p53 activation. Many studies showed that p53 cell-cycle and apoptosis functions are important for preventing tumor development. p53 also regulates many cellular processes including metabolism, antioxidant response, and DNA repair.

How is p53 regulated by MDM2?

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.

What activates p53 activity?

p53 is activated by a variety of cellular stresses, including DNA damage, hypoxia, and mitogenic oncogenes, but the extent to which each signal engages p53 as a tumour suppressor remains unknown.

How does p53 regulate gene expression?

p53 regulates transcription via two functionally specialized transactivation domains. p53 recognizes its DNA response elements by an elaborate mechanism involving a sequence-specific core DNA-binding domain and the regulatory C-terminal domain.

Are there any regulatory regions in the p53 gene?

p53 target genes are regulated in a stimulus-, locus-, and context-specific manner. In cell types A and B, both locus X and Y exhibit similar amounts of bound p53, however, their transcriptional output differs. Stress 1 is able to induce a cellular environment where coactivators A and B are available.

Which of the following are ways in which p53 regulates cellular function in the presence of DNA damage?

DNA damage and other stress signals may trigger the increase of p53 proteins, which have three major functions: growth arrest, DNA repair and apoptosis (cell death). The growth arrest stops the progression of cell cycle, preventing replication of damaged DNA.

How does p53 regulate 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 are the two roles of MDM2?

In this classic model, MDM2 directed p53 ubiquitination and degradation play the central role. However, emerging evidence suggests dual roles of MDM2 as a repressor of p53 activity. Ubiquitination dependent and ubiquitination independent mechanisms are jointly present to control p53 activity.

What is the function of MDM2?

Mdm2 is an important negative regulator of the p53 tumor suppressor. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain (TAD) of the p53 tumor suppressor and as an inhibitor of p53 transcriptional activation.

How does p53 regulates the cell cycle in the presence of damaged DNA?

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. In addition, p53 took on diverse roles to also directly impact the activity of various DNA-repair systems.