p53 and ATM: cell cycle, cell death, and cancer.
The development of a normal cell into a tumor cell appears to depend in part on mutations in genes that normally control cell cycle and cell death, thereby resulting in inappropriate cellular survival and tumorigenesis. ATM ("mutated in ataxia-telangiectasia") and p53 are two gene products that are believed to play a major role in maintaining the integrity of the genome such that alterations in these gene products may contribute to increased incidence of genomic changes such as deletions, translocations, and amplifications, which are common during oncogenesis. p53 is a critical participant in a signal transduction pathway that mediates either a G1 arrest or apoptosis in response to DNA damage. In addition, p53 is believed to be involved in the mitotic spindle checkpoint and in the regulation of centrosome function. Following certain cytotoxic stresses, normal ATM function is required for p53-mediated G1 arrest. ATM is also involved in other cellular processes such as S phase and G2-M phase arrest and in radiosensitivity. The understanding of the roles that both p53 and ATM play in cell cycle progression and cell death in response to DNA damage may provide new insights into the molecular mechanisms of cellular transformation and may help identify potential targets for improved cancer therapies.
Morgan
S E
SE
Johns Hopkins Oncology Center, Baltimore, Maryland 21205, USA.
Kastan
M B
MB
D000818:Animals; D017209:Apoptosis; D001260:Ataxia Telangiectasia / Q000503:physiopathology; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D016923:Cell Death; D004249:DNA Damage; D004268:DNA-Binding Proteins; D016158:Genes, p53; D006801:Humans; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000502:physiology*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human