Activation of the ATM kinase by ionizing radiation and phosphorylation of p53

Christine E. Canman; Dae Sik Lim; Karlene A. Cimprich; Yoichi Taya; Katsuyuki Tamai; Kazuyasu Sakaguchi; Ettore Appella; Michael B. Kastan; Janet D. Siliciano

doi:10.1126/science.281.5383.1677

Activation of the ATM kinase by ionizing radiation and phosphorylation of p53

Christine E. Canman, Dae Sik Lim, Karlene A. Cimprich, Yoichi Taya, Katsuyuki Tamai, Kazuyasu Sakaguchi, Ettore Appella, Michael B. Kastan, Janet D. Siliciano

School of Medicine

Research output: Contribution to journal › Article › peer-review

1633 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1677-1679
Number of pages	3
Journal	Science
Volume	281
Issue number	5383
DOIs	https://doi.org/10.1126/science.281.5383.1677
State	Published - Sep 11 1998

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title = "Activation of the ATM kinase by ionizing radiation and phosphorylation of p53",

abstract = "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.",

author = "Canman, {Christine E.} and Lim, {Dae Sik} and Cimprich, {Karlene A.} and Yoichi Taya and Katsuyuki Tamai and Kazuyasu Sakaguchi and Ettore Appella and Kastan, {Michael B.} and Siliciano, {Janet D.}",

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T1 - Activation of the ATM kinase by ionizing radiation and phosphorylation of p53

AU - Canman, Christine E.

AU - Lim, Dae Sik

AU - Cimprich, Karlene A.

AU - Taya, Yoichi

AU - Tamai, Katsuyuki

AU - Sakaguchi, Kazuyasu

AU - Appella, Ettore

AU - Kastan, Michael B.

AU - Siliciano, Janet D.

PY - 1998/9/11

Y1 - 1998/9/11

N2 - 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.

AB - 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.

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Activation of the ATM kinase by ionizing radiation and phosphorylation of p53

Abstract

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