Publication Date:
1998-09-11
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Canman, C E -- Lim, D S -- Cimprich, K A -- Taya, Y -- Tamai, K -- Sakaguchi, K -- Appella, E -- Kastan, M B -- Siliciano, J D -- CA71387/CA/NCI NIH HHS/ -- ES05777/ES/NIEHS NIH HHS/ -- New York, N.Y. -- Science. 1998 Sep 11;281(5383):1677-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Johns Hopkins School of Medicine, Oncology Center, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9733515" target="_blank"〉PubMed〈/a〉
Keywords:
Ataxia Telangiectasia Mutated Proteins
;
Cell Cycle Proteins
;
Cell Line
;
DNA Damage
;
DNA-Activated Protein Kinase
;
*DNA-Binding Proteins
;
Enzyme Activation
;
Humans
;
Lymphocytes/metabolism/radiation effects
;
Mutation
;
Nuclear Proteins
;
Phosphatidylinositol 3-Kinases/metabolism
;
Phosphorylation
;
Phosphoserine/metabolism
;
Protein Kinases/*metabolism
;
Protein-Serine-Threonine Kinases/metabolism
;
Proteins/genetics/*metabolism
;
*Radiation, Ionizing
;
Recombinant Fusion Proteins/metabolism
;
Recombinant Proteins/metabolism
;
Signal Transduction
;
Transfection
;
Tumor Suppressor Protein p53/*metabolism
;
Tumor Suppressor Proteins
;
Ultraviolet Rays
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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