title: ATM--a key determinant of multiple cellular responses to irradiation.
abstract: Ataxia-telangiectasia is a rare clinical disorder manifesting a variety of different abnormalities, including progressive neurodegeneration, increased cancer incidence, immune deficiency, sterility, and extreme radiosensitivity. Recent studies have demonstrated that the defective gene product in this disease, ATM, is a protein kinase. The identification of several different substrates for this kinase is beginning to explain the wide array of different physiologic abnormalities that occur when this gene product is dysfunctional. Since the ATM protein is a critical signaling molecule in the cellular response to ionizing irradiation, the identification of these substrates also results in elucidation of the steps involved in a number of different cellular signaling pathways initiated by irradiation. Such insights also result in the identification of potential new targets for enhancing the efficacy of radiation therapy.
authors.affiliation: Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA. michael.kastan@stjude.org
authors.forename: M B
authors.initials: MB
authors.lastname: Kastan
authors.forename: D S
authors.initials: DS
authors.lastname: Lim
authors.forename: S T
authors.initials: ST
authors.lastname: Kim
authors.forename: D
authors.initials: D
authors.lastname: Yang
mesh_terms: D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002470:Cell Survival; D004249:DNA Damage / Q000528:radiation effects*; D004268:DNA-Binding Proteins; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000494:pharmacology; D015398:Signal Transduction / Q000528:radiation effects; D025521:Tumor Suppressor Proteins
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