Distinct pathways have been identified that cause p53 activation, including ARF-dependent response to oncogene activation, ribosomal protein-mediated response to abnormal rRNA synthesis, and ATM-dependent response to DNA damage.

In the delayed response ATM phosphorylates the inhibitor of p53, MDM2, and p53, which is also phosphorylated by Chk2. The resulting activation and stabilization of p53 leads to an increased expression of Cdk inhibitor p21, which further helps to keep Cdk activity low and to maintain long-term cell cycle arrest.

Oct 7, 2022 · Many molecules mediating PTMs on p53 have been identified. The anticancer potential realized by targeting these molecules has been shown through experiments and clinical trials to sensitize...

Sep 11, 1998 · ATM phosphorylated p53 in vitro on a single residue, serine-15, which is phosphorylated in vivo in response to DNA damage. This activity was markedly enhanced within minutes after treatment of cells with a radiomimetic drug; …

Jan 23, 2024 · The presented model shows a novel interaction of ATM with the p53 mRNA and describes the link between DNA Damage Sensing with the downstream p53 activation pathways; supporting the rising functional implications of synonymous …

We show in this report that ATM induces p53 accumulation by phosphorylating the ubiquitin E3 ligase MDM2. Multiple ATM target sites near the MDM2 RING domain function in a redundant manner to provide robust DNA damage signalling.

The ATM gene (mutated in the disease ataxia telangiectasia) activates the p53 tumor suppressor protein in response to DNA damage, explaining the higher incidence of cancer in AT patients.

The understanding of the roles that both p53 and ATM play in cell cycle progression and cell death in response to DNA damage may provide new insights into the molecular mechanisms of cellular transformation and may help identify potential targets for improved cancer therapies.

In response to ionizing radiation (IR), ATM, the gene product mutated in ataxia telangiectasia, stabilizes and activates p53 through phosphorylation of Ser 15 and (indirectly) Ser 20.

In response to DNA damage, eukaryotic cells activate ATM-Chk2 and/or ATR-Chk1 to arrest the cell cycle and initiate DNA repair. We show that in the absence of p53, cells depend on a third cell cycle checkpoint pathway involving p38MAPK/MK2 …