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Science 12 May 2000:
Vol. 288. no. 5468, pp. 1053 - 1058
DOI: 10.1126/science.288.5468.1053
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Reports

Noxa, a BH3-Only Member of the Bcl-2 Family and Candidate Mediator of p53-Induced Apoptosis

Eri Oda, 1* Rieko Ohki, 1* Hideki Murasawa, 1 Jiro Nemoto, 1 Tsukasa Shibue, 1 Toshiharu Yamashita, 2 Takashi Tokino, 2 Tadatsugu Taniguchi, 1 † Nobuyuki Tanaka 1

A critical function of tumor suppressor p53 is the induction of apoptosis in cells exposed to noxious stresses. We report a previously unidentified pro-apoptotic gene, Noxa. Expression of Noxa induction in primary mouse cells exposed to x-ray irradiation was dependent on p53. Noxa encodes a Bcl-2 homology 3 (BH3)-only member of the Bcl-2 family of proteins; this member contains the BH3 region but not other BH domains. When ectopically expressed, Noxa underwent BH3 motif-dependent localization to mitochondria and interacted with anti-apoptotic Bcl-2 family members, resulting in the activation of caspase-9. We also demonstrate that blocking the endogenous Noxa induction results in the suppression of apoptosis. Noxa may thus represent a mediator of p53-dependent apoptosis.

1 Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
2 Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University School of Medicine, S1 W17, Chuo-Ku, Sapporo 060-8543, Japan.
*   These authors contributed equally to this report.

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MYC levels govern hematopoietic tumor type and latency in transgenic mice.
D. P. Smith, M. L. Bath, D. Metcalf, A. W. Harris, and S. Cory (2006)
Blood 108, 653-661
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BH3-only proapoptotic Bcl-2 family members Noxa and Puma mediate neural precursor cell death..
R. S. Akhtar, Y. Geng, B. J. Klocke, C. B. Latham, A. Villunger, E. M. Michalak, A. Strasser, S. L. Carroll, and K. A. Roth (2006)
J. Neurosci. 26, 7257-7264
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Bcl2's Flexible Loop Domain Regulates p53 Binding and Survival.
X. Deng, F. Gao, T. Flagg, J. Anderson, and W. S. May (2006)
Mol. Cell. Biol. 26, 4421-4434
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PUMA Dissociates Bax and Bcl-XL to Induce Apoptosis in Colon Cancer Cells.
L. Ming, P. Wang, A. Bank, J. Yu, and L. Zhang (2006)
J. Biol. Chem. 281, 16034-16042
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Inhibition of Glutathione Synthesis Overcomes Bcl-2-Mediated Topoisomerase Inhibitor Resistance and Induces Nonapoptotic Cell Death via Mitochondrial-Independent Pathway.
A. Yoshida, H. Takemura, H. Inoue, T. Miyashita, and T. Ueda (2006)
Cancer Res. 66, 5772-5780
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Multiple actions of pifithrin-{alpha} on doxorubicin-induced apoptosis in rat myoblastic H9c2 cells.
C. C. Chua, X. Liu, J. Gao, R. C. Hamdy, and B. H. L. Chua (2006)
Am J Physiol Heart Circ Physiol 290, H2606-H2613
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MDM2 antagonists activate p53 and synergize with genotoxic drugs in B-cell chronic lymphocytic leukemia cells.
L. Coll-Mulet, D. Iglesias-Serret, A. F. Santidrian, A. M. Cosialls, M. de Frias, E. Castano, C. Campas, M. Barragan, A. F. de Sevilla, A. Domingo, et al. (2006)
Blood 107, 4109-4114
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