What does acetylation of p53 do?
Acetylation has many important effects on p53. It increases p53 protein stability, binding to low affinity promoters, association with other proteins, antiviral activities, and is required for its checkpoint responses to DNA damage and activated oncogenes [39,40,41,42].
What is the normal function of p53?
Normal Function 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. The p53 protein is located in the nucleus of cells throughout the body, where it attaches (binds) directly to DNA.
What activates p53 gene?
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.
How does p53 regulate damaged DNA?
One way in which p53 is thought to potentiate genomic stability, and consequently inhibit tumorigenesis, is by initiating cell cycle arrest, thus allowing repair of damaged DNA prior to DNA synthesis or segregation of the genome.
Is p53 a tumor suppressor gene?
The p53 gene is a type of tumor suppressor gene. Also called TP53 gene and tumor protein p53 gene.
What happens when damaged DNA is detected?
Background. DNA damage, if unrepaired, may result in mutation or cell death. Therefore, cells have evolved complex signaling networks to carefully monitor the integrity of the genome during DNA replication, and to initiate cell cycle arrest, repair, or apoptotic responses if errors are detected.
What happens if p53 is damaged?
If the p53 gene is damaged, tumor suppression is severely reduced. People who inherit only one functional copy of p53 will most likely develop tumors in early adulthood, a disease known as Li-Fraumeni syndrome.
What proteins detect DNA?
Phosphorylated histone 2AX (γH2AX) protein The detection of γH2AX protein phosphorylated at Serine-139 allows an approach for detecting and quantifying DNA DSBs, as the number of Serine-139-γH2AX molecules is associated with the quantity of DNA damage (26), therefore it may be used as a marker of DSBs.
Does p53 repair 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.
What is acetylation of p53?
Acetylation of p53 is a complex process that involves many different proteins and multiple layers of regulation. Even after many years of research investigating the acetylation of p53 and its other post-translational modifications, many questions still remain.
Why does TIP60 acetylation of p53 cause apoptosis?
K120 acetylation of p53 by Tip60 is associated with the selective induction of apoptosis rather than cell cycle arrest [77,78]. This site-specific acetylation is required for p53 binding to the Bax(Bcl2-associated X protein) and PUMApromoters, as well as histone H4 acetylation at the PUMApromoter [77,78].
What is the role of p53 in tumor suppression?
The ability of p53 to induce apoptosis plays an important role in tumor suppression. Here, we describe a previously unknown posttranslational modification of the DNA-binding domain of p53. This modification, acetylation of lysine 120 (K120), occurs rapidly after DNA damage and is catalyzed by the MYST family acetyltransferases hMOF and TIP60.
When is SOX4 required for maximal p53 acetylation?
Specifically, RNAi analyses showed that Sox4 is required for maximal p53 acetylation (at K373 and K382), transcriptional activation and induction of cell cycle arrest and apoptosis following DNA damage.