ATM Signaling Pathway

ATM (Ataxia Telangiectasia Mutated Protein) belongs to a family of Kinases that have sequence homology to PI3K (Phosphoinositide 3-Kinase) and acts as a tumor suppressor.

ATM is a key regulator of multiple signaling cascades which respond to DNA strand breaks induced by damaging agents IR (Ionizing Radiation), radiometric agents or by normal processes. These responses involve the activation of cell cycle Chk factors (Checkpoints factors), DNA repair and Apoptosis. In addition, ATM appears to function as a 'caretaker', suppressing tumorigenesis in specific T cell lineages. Its downstream targets include Chk1 (Cell Cycle Checkpoint Kinase-1), Chk2 (Cell Cycle Checkpoint Kinase-2), tumor suppressors like p53 and BRCA (Breast Cancer), DNA repair factors like Rad50, Rad51, GADD45 (Growth Arrest and DNA-Damage-inducible), and other signaling molecules like c-Abl and NF-KappaB (Nuclear Factor-Kappa B).

ATM is activated by the MRE11 (Meiotic Recombination-11)–Rad50–NBS1 (Nijmegen Breakage Syndrome-1) complex or 53BP1. The former is thought to be recruited at the DSB (DNA Double Strand Breaks), whereas the latter is recruited at chromatin regions flanking the DNA DSB and extending up to a few megabases from the DSB. Once ATM is activated it phosphorylates multiple substrates.

Click gene symbol on the map to view ORF/cDNA clone.

Data source: KEGG, BioCarta