title: Cytoplasmic ATM protein kinase: an emerging therapeutic target for diabetes, cancer and neuronal degeneration.
abstract: Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by cerebellar ataxia and oculocutaneous telangiectasias. The gene mutated in this disease, Atm (A-T mutated), encodes a serine/threonine protein kinase that has been traditionally considered to be a nuclear protein controlling cell-cycle progression. However, many of the growth abnormalities observed in patients with A-T, including neuronal degeneration and insulin resistance, remain difficult to explain with nuclear localization of ATM. Here, recent advances in elucidating the cytoplasmic localization and function of ATM are reviewed. Particular attention is given to the role of ATM in insulin signaling and Akt activation. The potential for cytoplasmic ATM protein kinase to be an emerging therapeutic target for treating diabetes, cancer and neuronal degeneration is discussed.
authors.affiliation: The Sanford Project, Sanford Research/USD, Sanford Health, and The Department of Pediatrics, Sanford School of Medicine of The University of South Dakota, 2301 East 60th Street North, Sioux Falls, SD 57104, USA. Daqing.Yang@sanfordhealth.org
authors.forename: Da-Qing
authors.initials: DQ
authors.lastname: Yang
authors.forename: Marie-Jo
authors.initials: MJ
authors.lastname: Halaby
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Jody C
authors.initials: JC
authors.lastname: Hibma
authors.forename: Paul
authors.initials: P
authors.lastname: Burn
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics / Q000503:physiopathology*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000201:enzymology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases