Publication Date:
1998-09-11
Description:
The ATM protein, encoded by the gene responsible for the human genetic disorder ataxia telangiectasia (A-T), regulates several cellular responses to DNA breaks. ATM shares a phosphoinositide 3-kinase-related domain with several proteins, some of them protein kinases. A wortmannin-sensitive protein kinase activity was associated with endogenous or recombinant ATM and was abolished by structural ATM mutations. In vitro substrates included the translation repressor PHAS-I and the p53 protein. ATM phosphorylated p53 in vitro on a single residue, serine-15, which is phosphorylated in vivo in response to DNA damage. This activity was markedly enhanced within minutes after treatment of cells with a radiomimetic drug; the total amount of ATM remained unchanged. Various damage-induced responses may be activated by enhancement of the protein kinase activity of ATM.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Banin, S -- Moyal, L -- Shieh, S -- Taya, Y -- Anderson, C W -- Chessa, L -- Smorodinsky, N I -- Prives, C -- Reiss, Y -- Shiloh, Y -- Ziv, Y -- NS31763/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1998 Sep 11;281(5383):1674-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9733514" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Signal Transducing
;
Androstadienes/pharmacology
;
Ataxia Telangiectasia/metabolism
;
Ataxia Telangiectasia Mutated Proteins
;
*Carrier Proteins
;
Cell Cycle Proteins
;
Cell Line
;
*DNA Damage
;
DNA-Binding Proteins
;
Enzyme Inhibitors/pharmacology
;
Humans
;
Mutation
;
Phosphatidylinositol 3-Kinases/chemistry
;
Phosphoproteins/metabolism
;
Phosphorylation
;
Protein Kinase Inhibitors
;
Protein Kinases/chemistry/*metabolism
;
*Protein-Serine-Threonine Kinases
;
Proteins/antagonists & inhibitors/chemistry/genetics/*metabolism
;
Recombinant Proteins/metabolism
;
Tumor Cells, Cultured
;
Tumor Suppressor Protein p53/*metabolism
;
Tumor Suppressor Proteins
;
Zinostatin/pharmacology
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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