Ataxia Telangiectasia Mutated (ATM) is a serine/threonine protein kinase that is the master regulator of the DNA double-strand break (DSB) repair pathway. ATM is a key part of the cell cycle machinery that activates checkpoint signaling in response to DSBs, apoptosis, and genotoxic insults. ATM normally exists in its inactive state as a dimer or tetramer - upon DNA damage, it dissociates into monomers triggered by its own autophosphorylation. This activated state binds and acts upon a large variety of different signaling molecules ranging from ABL1, p53, BRCA1, and RAD9. Not surprisingly, given the wide range of binding partners, ATM has a varied host of functions including vesicle and protein transport, T-cell development, cell cycle control, and tumor suppression. Defects in ATM are found in diseases such as ataxia telangiectasia (AT), T-cell acute lymphoblastic leukemia (TALL), T-prolymphocytic leukemia (TPLL), and B-cell non-Hodgkin lymphomas (BNHL). In a detailed investigation of ATM’s role in fertility, Scherthan’s group used the ATM antibody in their in situ hybridization and immunofluorescence architecture mapping studies in ATM knockout mice (1).
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Immunocytochemistry/Immunofluorescence: ATM Antibody
Use of the ATM antibody in allowed Stracker, et al. to propose a “hit-and-run” genomic instability strategy employed by adenoviral oncoproteins (such as E4) through the targeting of cellular proteins within the concatamer Mre11-Rad50-NBS1 complex responsible for DSB and telomere maintenance (2). Lung cancer studies aimed at measuring the response of lung Cancer Stem Cells (CSCs) to the novel telomerase inhibitor MST312 required the ATM antibody for cell population characterization and profiles (3). The study results are promising that the MST312 mainly targets the intended CSCs and could be a novel single approach. Additionally, Yan’s group found that the RAC1 GTPase plays an essential role in irradiation-induced downstream signaling through ERK pathways and the resulting G2/M checkpoint halt (4). Their study relied upon the ATM antibody for monitoring cell survival and checkpoint responses. Most recent results in gastric adenocarcinoma cells subjected to chemotherapy (paclitaxel, cisplatin) using the ATM antibody seem to suggest that cell death modulation during mitosis may be an effective therapeutic strategy (5).
Novus Biologicals offers ATM reagents for your research needs including:
