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p53- and Drug-Induced Apoptotic Responses Mediated by BH3-Only Proteins Puma and Noxa
Andreas Villunger,1,2*Ewa M. Michalak,1Leigh Coultas,1Franziska Müllauer,2Günther Böck,2Michael J. Ausserlechner,2Jerry M. Adams,1Andreas Strasser1*
Apoptosis provoked by DNA damage requires the p53 tumor suppressor,but which of the many p53-regulated genes are required has remainedunknown. Two genes induced by this transcription factor, noxaand puma (bbc3), stand out, because they encode BH3-only proteins,proapoptotic members of the Bcl-2 family required to initiateapoptosis. In mice with either noxa or puma disrupted, we observeddecreased DNA damage–induced apoptosis in fibroblasts,although only loss of Puma protected lymphocytes from cell death.Puma deficiency also protected cells against diverse p53-independentcytotoxic insults, including cytokine deprivation and exposureto glucocorticoids, the kinase inhibitor staurosporine, or phorbolester. Hence, Puma and Noxa are critical mediators of the apoptoticresponses 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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Inaugural Article: Loss of hepatic NF-{kappa}B activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activation.
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
|Abstract »|Full Text »|PDF »
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
|Abstract »|Full Text »|PDF »
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
|Abstract »|Full Text »|PDF »
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
|Abstract »|Full Text »|PDF »
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 »
