Activation of the ATM kinase by ionizing radiation and phosphorylation of p53.
The p53 tumor suppressor protein is activated and phosphorylated on serine-15 in response to various DNA damaging agents. The gene product mutated in ataxia telangiectasia, ATM, acts upstream of p53 in a signal transduction pathway initiated by ionizing radiation. Immunoprecipitated ATM had intrinsic protein kinase activity and phosphorylated p53 on serine-15 in a manganese-dependent manner. Ionizing radiation, but not ultraviolet radiation, rapidly enhanced this p53-directed kinase activity of endogenous ATM. These observations, along with the fact that phosphorylation of p53 on serine-15 in response to ionizing radiation is reduced in ataxia telangiectasia cells, suggest that ATM is a protein kinase that phosphorylates p53 in vivo.
Canman
C E
CE
The Johns Hopkins School of Medicine, Oncology Center, Baltimore, MD 21205, USA.
Lim
D S
DS
Cimprich
K A
KA
Taya
Y
Y
Tamai
K
K
Sakaguchi
K
K
Appella
E
E
Kastan
M B
MB
Siliciano
J D
JD
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D004249:DNA Damage; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000528:radiation effects; D009154:Mutation; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011839:Radiation, Ionizing; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D014466:Ultraviolet Rays
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D010768:Phosphoserine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; C497263:PRKDC protein, human