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Originally published in Science Express on 18 September 2003
Science 7 November 2003:
Vol. 302. no. 5647, pp. 1036 - 1038
DOI: 10.1126/science.1090072
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Reports

p53- and Drug-Induced Apoptotic Responses Mediated by BH3-Only Proteins Puma and Noxa

Andreas Villunger,1,2* Ewa M. Michalak,1 Leigh Coultas,1 Franziska Müllauer,2 Günther Böck,2 Michael J. Ausserlechner,2 Jerry M. Adams,1 Andreas Strasser1*

Apoptosis provoked by DNA damage requires the p53 tumor suppressor, but which of the many p53-regulated genes are required has remained unknown. Two genes induced by this transcription factor, noxa and puma (bbc3), stand out, because they encode BH3-only proteins, proapoptotic members of the Bcl-2 family required to initiate apoptosis. In mice with either noxa or puma disrupted, we observed decreased DNA damage–induced apoptosis in fibroblasts, although only loss of Puma protected lymphocytes from cell death. Puma deficiency also protected cells against diverse p53-independent cytotoxic insults, including cytokine deprivation and exposure to glucocorticoids, the kinase inhibitor staurosporine, or phorbol ester. Hence, Puma and Noxa are critical mediators of the apoptotic responses induced by p53 and other agents.

1 The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
2 Institute for Pathophysiology, University of Innsbruck, Austria.

* To whom correspondence should be addressed. E-mail: strasser{at}wehi.edu.au (A.S.) and andreas.villunger{at}uibk.ac.at (A.V.)

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   Abstract »    Full Text »    PDF »
Acetylation of Mouse p53 at Lysine 317 Negatively Regulates p53 Apoptotic Activities after DNA Damage..
C. Chao, Z. Wu, S. J. Mazur, H. Borges, M. Rossi, T. Lin, J. Y. J. Wang, C. W. Anderson, E. Appella, and Y. Xu (2006)
Mol. Cell. Biol. 26, 6859-6869
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Specific Contribution of p19ARF to Nitric Oxide-Dependent Apoptosis..
M. Zeini, P. G. Traves, R. Lopez-Fontal, C. Pantoja, A. Matheu, M. Serrano, L. Bosca, and S. Hortelano (2006)
J. Immunol. 177, 3327-3336
   Abstract »    Full Text »    PDF »
Cell death provoked by loss of interleukin-3 signaling is independent of Bad, Bim, and PI3 kinase, but depends in part on Puma.
P. G. Ekert, A. M. Jabbour, A. Manoharan, J. E. Heraud, J. Yu, M. Pakusch, E. M. Michalak, P. N. Kelly, B. Callus, T. Kiefer, et al. (2006)
Blood 108, 1461-1468
   Abstract »    Full Text »    PDF »
The NF-{kappa}B regulator Bcl-3 and the BH3-only proteins Bim and Puma control the death of activated T cells.
A. Bauer, A. Villunger, V. Labi, S. F. Fischer, A. Strasser, H. Wagner, R. M. Schmid, and G. Hacker (2006)
PNAS 103, 10979-10984
   Abstract »    Full Text »    PDF »
Inaugural Article: Loss of hepatic NF-{kappa}B activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation.
T. Sakurai, S. Maeda, L. Chang, and M. Karin (2006)
PNAS 103, 10544-10551
   Abstract »    Full Text »    PDF »
FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal.
H. You, M. Pellegrini, K. Tsuchihara, K. Yamamoto, G. Hacker, M. Erlacher, A. Villunger, and T. W. Mak (2006)
J. Exp. Med. 203, 1657-1663
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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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Targeted deletion of Puma attenuates cardiomyocyte death and improves cardiac function during ischemia-reperfusion.
A. Toth, J. R. Jeffers, P. Nickson, J.-Y. Min, J. P. Morgan, G. P. Zambetti, and P. Erhardt (2006)
Am J Physiol Heart Circ Physiol 291, H52-H60
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
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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Identification of a Novel Germ Line Variant Hotspot Mutant p53-R175L in Pediatric Adrenal Cortical Carcinoma..
A. N. West, R. C. Ribeiro, J. Jenkins, C. Rodriguez-Galindo, B. C. Figueiredo, R. Kriwacki, and G. P. Zambetti (2006)
Cancer Res. 66, 5056-5062
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Genome-Wide Analysis of p53 under Hypoxic Conditions..
E. M. Hammond, D. J. Mandell, A. Salim, A. J. Krieg, T. M. Johnson, H. A. Shirazi, L. D. Attardi, and A. J. Giaccia (2006)
Mol. Cell. Biol. 26, 3492-3504
   Abstract »    Full Text »    PDF »
Roles of Apoptosis in Airway Epithelia.
Y. Tesfaigzi (2006)
Am. J. Respir. Cell Mol. Biol. 34, 537-547
   Abstract »    Full Text »    PDF »
PUMA Sensitizes Lung Cancer Cells to Chemotherapeutic Agents and Irradiation..
J. Yu, W. Yue, B. Wu, and L. Zhang (2006)
Clin. Cancer Res. 12, 2928-2936
   Abstract »    Full Text »    PDF »
Endoplasmic Reticulum Stress-induced Apoptosis: MULTIPLE PATHWAYS AND ACTIVATION OF p53-UP-REGULATED MODULATOR OF APOPTOSIS (PUMA) AND NOXA BY p53.
J. Li, B. Lee, and A. S. Lee (2006)
J. Biol. Chem. 281, 7260-7270
   Abstract »    Full Text »    PDF »


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