Cytoplasmic ATM protein kinase: an emerging therapeutic target for diabetes, cancer and neuronal degeneration

The role of oxidized ATM in the regulation of oxidative stress-induced energy metabolism reprogramming of CAFs

“…Hypoxia-induced OS causes the EMR of myocardial cells and brain cells in ischemic diseases including myocardial or cerebral infarction. Loss of function of ATM leads to the inhibition of the insulin pathway, insulin resistance, and decrease of glucose uptake [94,95]. So, based on the facts that the EMR was observed in the CAFs and oxidized ATM was widely involved in the cellular glucose metabolism, we guess that ATM may also be a key regulator of the CAFs' EMR.…”

“…Under the condition of insulin stimulus, the active AKT is responsible for GLUT4 translocation from the cytosol to the plasma membrane and glucose uptake in muscle cells [94]. The mTORC1 signaling pathway is a most frequently dysregulated signaling cascade in cancers resulting from activation of proto-oncogenes and loss of tumor suppressors.…”

ATM Protein Kinase Signaling, Type 2 Diabetes and Cardiovascular Disease

“…The disease affects 1 in 40 000 to 1 in 200 000 individuals globally, with an estimated 2.8 % of the global population being A-T carriers [3,4]. The most prominent characteristics of A-T are cerebellar neurodegeneration, oculocutaneous telangiectasia, immunodeficiency, a high risk for cancer, premature ageing and radiosensitivity [2,5,6]. Patients also display growth retardation, insulin resistance and glucose intolerance [6].…”

“…The most prominent characteristics of A-T are cerebellar neurodegeneration, oculocutaneous telangiectasia, immunodeficiency, a high risk for cancer, premature ageing and radiosensitivity [2,5,6]. Patients also display growth retardation, insulin resistance and glucose intolerance [6]. Carriers of the disease were found to die approximately 4 years earlier than non-carriers due to the development of cancer and approximately 11 years earlier due to ischemic heart disease [2,7].…”

Molecular Bases of Ataxia Telangiectasia: One Kinase Multiple Functions

“…Finally, although ATM is primarily localized to the nucleus, it has been shown that a minor fraction of the protein is present in the cytoplasm of various cell types [24]. First evidence for a cytoplasmic form is the discovery of ATM association with both peroxisomes and endosomes [25,26].…”