ATM dependent apoptosis in the nervous system.
Ataxia-telangiectasia is a human syndrome resulting from mutations of the ATM protein kinase that is characterized by radiation sensitivity and neurodegeneration. Although neuroprotective, the molecular details of ATM function in the nervous system are uncertain. However, in the mouse, Atm is essential for ionizing radiation-induced apoptosis in select postmitotic populations of the developing nervous system. Atm-dependent apoptosis in the nervous system also requires p53, consistent with the well-established link of p53 as a major substrate of ATM. Furthermore, the proapoptotic effector Bax is also required for most, but not all, Atm-dependent apoptosis. Therefore, after DNA damage in the developing nervous system, Atm initiates a p53-dependent apoptotic cascade in differentiating neural cells. Together, these data suggest ATM-dependent apoptosis may be important for elimination of neural cells that have accumulated genomic damage during development, thus preventing dysfunction of these cells later in life.
Lee
Y
Y
Department of Genetics, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
McKinnon
P J
PJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002490:Central Nervous System / Q000002:abnormalities* / Q000378:metabolism / Q000503:physiopathology; D004268:DNA-Binding Proteins; D006801:Humans; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases