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Science 30 September 1994:
Vol. 265. no. 5181, pp. 2091 - 2093
DOI: 10.1126/science.8091232

Articles

Science, Vol 265, Issue 5181, 2091-2093
Copyright © 1994 by American Association for the Advancement of Science


articles

Mediation of c-Myc-induced apoptosis by p53

H Hermeking and D Eick

Institut fur Klinische Molekularbiologie und Tumorgenetik Forschungszentrum fur Umwelt und Gesundheit, GSF, Munchen, Germany.

The cellular proto-oncogene c-myc is involved in cell proliferation and transformation but is also implicated in the induction of programmed cell death (apoptosis). The same characteristics have been described for the tumor suppressor gene p53, the most commonly mutated gene in human cancer. In quiescent mouse fibroblasts expressing wild-type p53 protein, activation of c-Myc was found to induce apoptosis and cell cycle reentry, preceded by stabilization of p53. In contrast, in quiescent p53-null fibroblasts, activation of c-Myc induced cell cycle reentry but not apoptosis. These results suggest that p53 mediates apoptosis as a safeguard mechanism to prevent cell proliferation induced by oncogene activation.


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c-Myc Controls Proliferation Versus Differentiation in Human Pancreatic Endocrine Cells.
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J. Clin. Endocrinol. Metab. 87, 3475-3485
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Inactivation of E2f1 Enhances Tumorigenesis in a Myc Transgenic Model.
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PNAS 99, 6274-6279
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Identification of Myc-mediated Death Response Pathways by Microarray Analysis.
Q. Yu, M. He, N. H. Lee, and E. T. Liu (2002)
J. Biol. Chem. 277, 13059-13066
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Differential Effects of p21WAF1/CIP1 Deficiency on MMTV-ras and MMTV-myc Mammary Tumor Properties.
D. J. Bearss, R. J. Lee, D. A. Troyer, R. G. Pestell, and J. J. Windle (2002)
Cancer Res. 62, 2077-2084
   Abstract »    Full Text »    PDF »
Loss of Bax Alters Tumor Spectrum and Tumor Numbers in ARF-deficient Mice.
C. M. Eischen, J. E. Rehg, S. J. Korsmeyer, and J. L. Cleveland (2002)
Cancer Res. 62, 2184-2191
   Abstract »    Full Text »    PDF »
c-myc-induced Apoptosis in Polycystic Kidney Disease Is Independent of FasL/Fas Interaction.
M. Couillard, R. Guillaume, N. Tanji, V. D'Agati, and M. Trudel (2002)
Cancer Res. 62, 2210-2214
   Abstract »    Full Text »    PDF »
SIV-associated Lymphomas in Rhesus Monkeys (Macaca mulatta) in Comparison with HIV-associated Lymphomas.
K. Kahnt, K. Matz-Rensing, P. Hofmann, C. Stahl-Hennig, and F.-J. Kaup (2002)
Vet. Pathol. 39, 42-55
   Abstract »    Full Text »    PDF »
Receptor- and mitochondrial-mediated apoptosis in acute leukemia: a translational view.
A. D. Schimmer, D. W. Hedley, L. Z. Penn, and M. D. Minden (2001)
Blood 98, 3541-3553
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c-Myc Is Necessary for DNA Damage-Induced Apoptosis in the G2 Phase of the Cell Cycle.
S. Adachi, A. J. Obaya, Z. Han, N. Ramos-Desimone, J. H. Wyche, and J. M. Sedivy (2001)
Mol. Cell. Biol. 21, 4929-4937
   Abstract »    Full Text »    PDF »
C-Myc Down-Regulation Increases Susceptibility to Cisplatin through Reactive Oxygen Species-Mediated Apoptosis in M14 Human Melanoma Cells.
A. Biroccio, B. Benassi, S. Amodei, C. Gabellini, D. Del Bufalo, and G. Zupi (2001)
Mol. Pharmacol. 60, 174-182
   Abstract »    Full Text »
Involvement of p38 in Apoptosis-associated Membrane Blebbing and Nuclear Condensation.
R. G. Deschesnes, J. Huot, K. Valerie, and J. Landry (2001)
Mol. Biol. Cell 12, 1569-1582
   Abstract »    Full Text »    PDF »
DNA-damaging carcinogen 3-amino-1,4-dimethyl-5H-pyrido [4,3-b]indole (Trp-P-1) induces apoptosis via caspase-9 in primary cultured rat hepatocytes.
B. Shiotani, Y. Nonaka, T. Hashimoto, K. Kihara, K. Kanazawa, G.-i. Danno, and H. Ashida (2001)
Carcinogenesis 22, 693-700
   Abstract »    Full Text »    PDF »
Targeted Deletion of the S-Phase-Specific Myc Antagonist Mad3 Sensitizes Neuronal and Lymphoid Cells to Radiation-Induced Apoptosis.
C. Quéva, G. A. McArthur, B. M. Iritani, and R. N. Eisenman (2001)
Mol. Cell. Biol. 21, 703-712
   Abstract »    Full Text »
Role of NF-{kappa}B and Myc Proteins in Apoptosis Induced by Hepatitis B Virus HBx Protein.
F. Su, C. N. Theodosis, and R. J. Schneider (2001)
J. Virol. 75, 215-225
   Abstract »    Full Text »
v-Src Generates a p53-Independent Apoptotic Signal.
B. L. Webb, E. Jimenez, and G. S. Martin (2000)
Mol. Cell. Biol. 20, 9271-9280
   Abstract »    Full Text »
Ablation of the Retinoblastoma gene family deregulates G1 control causing immortalization and increased cell turnover under growth-restricting conditions.
J.-H. Dannenberg, A. van Rossum, L. Schuijff, and H. te Riele (2000)
Genes & Dev. 14, 3051-3064
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Molecular Biology of Burkitt's Lymphoma.
J. L. Hecht and J. C. Aster (2000)
J. Clin. Oncol. 18, 3707-3721
   Abstract »    Full Text »    PDF »
Proapoptotic p53-Interacting Protein 53BP2 Is Induced by UV Irradiation but Suppressed by p53.
C. D. Lopez, Y. Ao, L. H. Rohde, T. D. Perez, D. J. O'Connor, X. Lu, J. M. Ford, and L. Naumovski (2000)
Mol. Cell. Biol. 20, 8018-8025
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Bax Is a Transcriptional Target and Mediator of c-Myc-induced Apoptosis.
K. O. Mitchell, M. S. Ricci, T. Miyashita, D. T. Dicker, Z. Jin, J. C. Reed, and W. S. El-Deiry (2000)
Cancer Res. 60, 6318-6325
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A Modified p53 Overcomes mdm2-mediated Oncogenic Transformation: A Potential Cancer Therapeutic Agent.
J. Lin, X. Jin, C. Page, V. K. Sondak, G. Jiang, and R. K. Reynolds (2000)
Cancer Res. 60, 5895-5901
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Induction of Cell Cycle Progression and Acceleration of Apoptosis Are Two Separable Functions of c-Myc: Transrepression Correlates with Acceleration of Apoptosis.
S. D. Conzen, K. Gottlob, E. S. Kandel, P. Khanduri, A. J. Wagner, M. O'Leary, and N. Hay (2000)
Mol. Cell. Biol. 20, 6008-6018
   Abstract »    Full Text »
Different Combinations of Genetic/Epigenetic Alterations Inactivate the p53 and pRb Pathways in Invasive Human Bladder Cancers.
S. Sarkar, K. P. Jülicher, M. S. Burger, V. Della Valle, C.-J. Larsen, T. R. Yeager, T. B. Grossman, R. W. Nickells, C. Protzel, D. F. Jarrard, et al. (2000)
Cancer Res. 60, 3862-3871
   Abstract »    Full Text »
Expression of Fas Ligand in Activated T Cells Is Regulated by c-Myc.
T. Brunner, S. Kasibhatla, M. J. Pinkoski, C. Frutschi, N. J. Yoo, F. Echeverri, A. Mahboubi, and D. R. Green (2000)
J. Biol. Chem. 275, 9767-9772
   Abstract »    Full Text »    PDF »
PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family.
L. D. Attardi, E. E. Reczek, C. Cosmas, E. G. Demicco, M. E. McCurrach, S. W. Lowe, and T. Jacks (2000)
Genes & Dev. 14, 704-718
   Abstract »    Full Text »
Apoptosis in cancer.
S. W. Lowe and A. W. Lin (2000)
Carcinogenesis 21, 485-495
   Abstract »    Full Text »    PDF »
Activated Notch1 Modulates Gene Expression in B Cells Similarly to Epstein-Barr Viral Nuclear Antigen 2.
L. J. Strobl, H. Höfelmayr, G. Marschall, M. Brielmeier, G. W. Bornkamm, and U. Zimber-Strobl (2000)
J. Virol. 74, 1727-1735
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Genetic Instability, Oncogenes, and the p53 Pathway.
G. WAHL and O. VAFA (2000)
Cold Spring Harb Symp Quant Biol 65, 511-520
   Abstract »    PDF »
Regulation of the p53 Tumor Suppressor Protein.
M. Oren (1999)
J. Biol. Chem. 274, 36031-36034
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p53 Inhibits {alpha}6{beta}4 Integrin Survival Signaling by Promoting the Caspase 3-dependent Cleavage of AKT/PKB.
R. E. Bachelder, M. J. Ribick, A. Marchetti, R. Falcioni, S. Soddu, K. R. Davis, and A. M. Mercurio (1999)
J. Cell Biol. 147, 1063-1072
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INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53.
C. A. Schmitt, M. E. McCurrach, E. de Stanchina, R. R. Wallace-Brodeur, and S. W. Lowe (1999)
Genes & Dev. 13, 2670-2677
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Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF.
J. J.L. Jacobs, B. Scheijen, J.-W. Voncken, K. Kieboom, A. Berns, and M. van Lohuizen (1999)
Genes & Dev. 13, 2678-2690
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twist is a potential oncogene that inhibits apoptosis.
R. Maestro, A. P. D. Tos, Y. Hamamori, S. Krasnokutsky, V. Sartorelli, L. Kedes, C. Doglioni, D. H. Beach, and G. J. Hannon (1999)
Genes & Dev. 13, 2207-2217
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Thiol Depletion Induces Apoptosis in Cultured Lung Fibroblasts.
K. Aoshiba, S. Yasui, K. Nishimura, and A. Nagai (1999)
Am. J. Respir. Cell Mol. Biol. 21, 54-64
   Abstract »    Full Text »
Btf, a Novel Death-Promoting Transcriptional Repressor That Interacts with Bcl-2-Related Proteins.
G. M. Kasof, L. Goyal, and E. White (1999)
Mol. Cell. Biol. 19, 4390-4404
   Abstract »    Full Text »    PDF »
c-Myc-induced sensitization to apoptosis is mediated through cytochrome c release.
P. Juin, A.-O. Hueber, T. Littlewood, and G. Evan (1999)
Genes & Dev. 13, 1367-1381
   Abstract »    Full Text »
Biochemical and Genetic Control of Apoptosis: Relevance to Normal Hematopoiesis and Hematological Malignancies.
R. G. Wickremasinghe and A. V. Hoffbrand (1999)
Blood 93, 3587-3600
   Full Text »    PDF »
Nuclear Factor kappa B Nuclear Translocation Upregulates c-Myc and p53 Expression during NMDA Receptor-Mediated Apoptosis in Rat Striatum.
Z.-H. Qin, R.-W. Chen, Y. Wang, M. Nakai, D.-M. Chuang, and T. N. Chase (1999)
J. Neurosci. 19, 4023-4033
   Abstract »    Full Text »    PDF »
Loss of the ARF Tumor Suppressor Reverses Premature Replicative Arrest but not Radiation Hypersensitivity Arising from Disabled Atm Function.
T. Kamijo, E. van de Kamp, M. J. Chong, F. Zindy, J. A. Diehl, C. J. Sherr, and P. J. McKinnon (1999)
Cancer Res. 59, 2464-2469
   Abstract »    Full Text »    PDF »
cdc25A Is Necessary but Not Sufficient for Optimal c-myc–Induced Apoptosis and Cell Proliferation of Vascular Smooth Muscle Cells.
K. Macdonald and M. R. Bennett (1999)
Circ. Res. 84, 820-830
   Abstract »    Full Text »    PDF »
Apaf-1 and Caspase-9 in p53-Dependent Apoptosis and Tumor Inhibition.
M. S. Soengas, R. M. Alarcón, H. Yoshida, A. J. Giaccia, R. Hakem, T. W. Mak, and S. W. Lowe (1999)
Science 284, 156-159
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Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor.
T. Nomura, M. M. Khan, S. C. Kaul, H.-D. Dong, R. Wadhwa, C. Colmenares, I. Kohno, and S. Ishii (1999)
Genes & Dev. 13, 412-423
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High Affinity Insertion/Deletion Lesion Binding by p53. EVIDENCE FOR A ROLE OF THE p53 CENTRAL DOMAIN.
S. T. Szak and J. A. Pietenpol (1999)
J. Biol. Chem. 274, 3904-3909
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Expression of Apoptosis-related Genes in Human Head and Neck Squamous Cell Carcinomas Undergoing p53-mediated Programmed Cell Death.
M. J. Frederick, P. R. Holton, M. Hudson, M. Wang, and G. L. Clayman (1999)
Clin. Cancer Res. 5, 361-369
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Induction of Programmed Cell Death in Kaposi's Sarcoma Cells by Preparations of Human Chorionic Gonadotropin.
F. Samaniego, J. L. Bryant, N. Liu, J. E. Karp, A. L. Sabichi, A. Thierry, Y. Lunardi-Iskandar, and R. C. Gallo (1999)
J Natl Cancer Inst 91, 135a-143a
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p53-independent apoptosis induced by muscle differentiation stimuli in polyomavirus large T-expressing myoblasts.
V Gottifredi, A Peschiaroli, G. Fimia, and R Maione (1999)
J. Cell Sci. 112, 2397-2407
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c-Myc Target Genes Involved in Cell Growth, Apoptosis, and Metabolism.
C. V. Dang (1999)
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Alveolar macrophage apoptosis and TNF-alpha , but not p53, expression correlate with murine response to bleomycin.
L. A. Ortiz, K. Moroz, J.-Y. Liu, G. W. Hoyle, T. Hammond, R. F. Hamilton, A. Holian, W. Banks, A. R. Brody, and M. Friedman (1998)
Am J Physiol Lung Cell Mol Physiol 275, L1208-L1218
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Thioredoxin Reductase Mediates Cell Death Effects of the Combination of Beta Interferon and Retinoic Acid.
E. R. Hofman, M. Boyanapalli, D. J. Lindner, X. Weihua, B. A. Hassel, R. Jagus, P. L. Gutierrez, and D. V. Kalvakolanu (1998)
Mol. Cell. Biol. 18, 6493-6504
   Abstract »    Full Text »
Adenovirus-Mediated Expression of a Dominant Negative Mutant of p65/RelA Inhibits Proinflammatory Gene Expression in Endothelial Cells Without Sensitizing to Apoptosis.
M. P. Soares, A. Muniappan, E. Kaczmarek, K. Koziak, C. J. Wrighton, F. Steinhauslin, C. Ferran, H. Winkler, F. H. Bach, and J. Anrather (1998)
J. Immunol. 161, 4572-4582
   Abstract »    Full Text »    PDF »
The complexity of p53 modulation: emerging patterns from divergent signals.
A. J. Giaccia and M. B. Kastan (1998)
Genes & Dev. 12, 2973-2983
   Full Text »
Tumor surveillance via the ARF-p53 pathway.
C. J. Sherr (1998)
Genes & Dev. 12, 2984-2991
   Full Text »
A Matter of Life and Cell Death.
G. Evan and T. Littlewood (1998)
Science 281, 1317-1322
   Abstract »    Full Text »
Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization.
F. Zindy, C. M. Eischen, D. H. Randle, T. Kamijo, J. L. Cleveland, C. J. Sherr, and M. F. Roussel (1998)
Genes & Dev. 12, 2424-2433
   Abstract »    Full Text »
E1A signaling to p53 involves the p19ARF tumor suppressor.
E. de Stanchina, M. E. McCurrach, F. Zindy, S.-Y. Shieh, G. Ferbeyre, A. V. Samuelson, C. Prives, M. F. Roussel, C. J. Sherr, and S. W. Lowe (1998)
Genes & Dev. 12, 2434-2442
   Abstract »    Full Text »
Distinct Apoptotic Responses Imparted by c-myc and max.
C. E. Nesbit, S. Fan, H. Zhang, and E. V. Prochownik (1998)
Blood 92, 1003-1010
   Abstract »    Full Text »    PDF »
Apoptosis : Basic Mechanisms and Implications for Cardiovascular Disease.
A. Haunstetter and S. Izumo (1998)
Circ. Res. 82, 1111-1129
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The molecular role of Myc in growth and transformation: recent discoveries lead to new insights.
L. Facchini and L. Z. Penn (1998)
FASEB J 12, 633-651
   Abstract »    Full Text »
Roles of the Tumor Suppressor p53 and the Cyclin-dependent Kinase Inhibitor p21WAF1/CIP1 in Receptor-mediated Apoptosis of WEHI 231 B Lymphoma Cells.
M. Wu, R. E. Bellas, J. Shen, and G. E. Sonenshein (1998)
J. Exp. Med. 187, 1671-1679
   Abstract »    Full Text »    PDF »
Identification of Positive and Negative Regulatory Regions Involved in Regulating Expression of the Human Cytomegalovirus UL94 Late Promoter: Role of IE2-86 and Cellular p53 in Mediating Negative Regulatory Function.
B. A. Wing, R. A. Johnson, and E.-S. Huang (1998)
J. Virol. 72, 1814-1825
   Abstract »    Full Text »    PDF »
p16/INK4a and p15/INK4b Gene Methylation and Absence of p16/INK4a mRNA and Protein Expression in Burkitt's Lymphoma.
U. Klangby, I. Okan, K. P. Magnusson, M. Wendland, P. Lind, and K. G. Wiman (1998)
Blood 91, 1680-1687
   Abstract »    Full Text »    PDF »
A unique glucose-dependent apoptotic pathway induced by c-Myc.
H. Shim, Y. S. Chun, B. C. Lewis, and C. V. Dang (1998)
PNAS 95, 1511-1516
   Abstract »    Full Text »    PDF »
Characterization of the p53-Dependent Postmitotic Checkpoint following Spindle Disruption.
J. S. Lanni and T. Jacks (1998)
Mol. Cell. Biol. 18, 1055-1064
   Abstract »    Full Text »



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