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Science 11 September 1998:
Vol. 281. no. 5383, pp. 1677 - 1679
DOI: 10.1126/science.281.5383.1677
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Reports

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, *dagger Janet D. Siliciano

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.

C. E. Canman, D.-S. Lim, M. B. Kastan, J. D. Siliciano, The Johns Hopkins School of Medicine, Oncology Center, Baltimore, MD 21205, USA. K. A. Cimprich, Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305, USA. Y. Taya, National Cancer Center Research Institute, Tsukiji 5-chome, Chuo-ku, Tokyo 104, Japan. K. Tamai, Ina Laboratories, MBL Co. Ltd., Ina, Nagano 396, Japan. K. Sakaguchi and E. Appella, Laboratory of Cell Biology, National Institutes of Health, Bethesda, MD 20892, USA.
*   Present address: Department of Hematology-Oncology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, D-1034, Memphis, TN 38105-2794, USA.

dagger    To whom correspondence should be addressed. E-mail: Michael.Kastan{at}stjude.org

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Mol. Biol. Cell 17, 1583-1592
   Abstract »    Full Text »    PDF »
Disruption of G1-phase phospholipid turnover by inhibition of Ca2+-independent phospholipase A2 induces a p53-dependent cell-cycle arrest in G1 phase.
X. H. Zhang, C. Zhao, K. Seleznev, K. Song, J. J. Manfredi, and Z. A. Ma (2006)
J. Cell Sci. 119, 1005-1015
   Abstract »    Full Text »    PDF »
Inhibition of the ATM/p53 Signal Transduction Pathway by Kaposi's Sarcoma-Associated Herpesvirus Interferon Regulatory Factor 1.
Y. C. Shin, H. Nakamura, X. Liang, P. Feng, H. Chang, T. F. Kowalik, and J. U. Jung (2006)
J. Virol. 80, 2257-2266
   Abstract »    Full Text »    PDF »
DNA Damage during Reoxygenation Elicits a Chk2-Dependent Checkpoint Response..
R. A. Freiberg, E. M. Hammond, M. J. Dorie, S. M. Welford, and A. J. Giaccia (2006)
Mol. Cell. Biol. 26, 1598-1609
   Abstract »    Full Text »    PDF »
ATM Requirement in Gene Expression Responses to Ionizing Radiation in Human Lymphoblasts and Fibroblasts.
C. L. Innes, A. N. Heinloth, K. G. Flores, S. O. Sieber, P. B. Deming, P. R. Bushel, W. K. Kaufmann, and R. S. Paules (2006)
Mol. Cancer Res. 4, 197-207
   Abstract »    Full Text »    PDF »
ATM promotes apoptosis and suppresses tumorigenesis in response to Myc.
R. V. Pusapati, R. J. Rounbehler, S. Hong, J. T. Powers, M. Yan, K. Kiguchi, M. J. McArthur, P. K. Wong, and D. G. Johnson (2006)
PNAS 103, 1446-1451
   Abstract »    Full Text »    PDF »
DNA Replication Stress-induced Phosphorylation of Cyclic AMP Response Element-binding Protein Mediated by ATM.
G. E. Dodson and R. S. Tibbetts (2006)
J. Biol. Chem. 281, 1692-1697
   Abstract »    Full Text »    PDF »
DNA damage checkpoints in mammals.
H. Niida and M. Nakanishi (2006)
Mutagenesis 21, 3-9
   Abstract »    Full Text »    PDF »
mTOR{middle dot}RICTOR Is the Ser473 Kinase for Akt/Protein Kinase B in 3T3-L1 Adipocytes.
R. C. Hresko and M. Mueckler (2005)
J. Biol. Chem. 280, 40406-40416
   Abstract »    Full Text »    PDF »
Tachpyridine, a metal chelator, induces G2 cell-cycle arrest, activates checkpoint kinases, and sensitizes cells to ionizing radiation.
J. Turner, C. Koumenis, T. E. Kute, R. P. Planalp, M. W. Brechbiel, D. Beardsley, B. Cody, K. D. Brown, F. M. Torti, and S. V. Torti (2005)
Blood 106, 3191-3199
   Abstract »    Full Text »    PDF »
Adenosine Monophosphate-Activated Protein Kinase Suppresses Vascular Smooth Muscle Cell Proliferation Through the Inhibition of Cell Cycle Progression.
M. Igata, H. Motoshima, K. Tsuruzoe, K. Kojima, T. Matsumura, T. Kondo, T. Taguchi, K. Nakamaru, M. Yano, D. Kukidome, et al. (2005)
Circ. Res. 97, 837-844
   Abstract »    Full Text »    PDF »
A plausible model for the digital response of p53 to DNA damage.
L. Ma, J. Wagner, J. J. Rice, W. Hu, A. J. Levine, and G. A. Stolovitzky (2005)
PNAS 102, 14266-14271
   Abstract »    Full Text »    PDF »
Overexpression of 15-Lipoxygenase-1 Induces Growth Arrest through Phosphorylation of p53 in Human Colorectal Cancer Cells.
J.-S. Kim, S. J. Baek, F. G. Bottone Jr., T. Sali, and T. E. Eling (2005)
Mol. Cancer Res. 3, 511-517
   Abstract »    Full Text »    PDF »


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