THE MANY ROLES OF c-Myc IN APOPTOSIS
Abstract
▪ Abstract The proto-oncogene c-myc encodes a transcription factor c-Myc, which is of great importance in controlling cell growth and vitality. The quantity of c-Myc is carefully controlled by many mechanisms, and its actions to induce and repress genes are modulated by interactions with other regulatory proteins. Understanding the kinetic and quantitative relationships that determine how and what genes c-Myc regulates is essential to understanding how Myc is involved in apoptosis. Reduction of c-myc expression and its inappropriate expression can be associated with cellular apoptosis. This review outlines the nature and regulation of the c-myc gene and of c-Myc and presents the systems and conditions in which Myc-related apoptotic events occur. Hypotheses of the mechanisms by which expression and repression of c-myc lead to apoptosis are discussed.
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Approximately 70% of human cancers involve dysregulated MYC expression.
“Research indicates that approximately 70% of human cancers involve dysregulated MYC expression.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [515]
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Murine c-myc retroviruses alter the growth requirements of myeloid cell lines.
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Modulation of cytotoxicity of chemotherapeutic drugs by activated H-γas
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Self-citationOverexpression of c-Fos induces apoptosis of CD43+ pro-B cells
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Mutant H-ras overexpression inhibits drug and U.V. induced apoptosis.
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Combination Anti-Gene Therapy Targeting c-myc and p53 in Ovarian Cancer Cell Lines
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Antitumor Effects of Antisense Phosphorothioate c-myc Oligodeoxynucleotides: a Question of Mechanism
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Role of c-myc and CD45 in spontaneous and anti-receptor-induced apoptosis in adult murine B cells
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Glucocorticoid regulation of c-myc promoter utilization in P1798 T-lymphoma cells.
Ma, T., Mahajan, P. B., & Thompson, E. A. (1992) · Molecular Endocrinology · doi:10.1210/mend.6.6.1495494 · Cited by 16 · see citing works
Self-citationExogenous c-myc gene overexpression interferes with early events in F9 cell differentiation.
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Self-citationIn vivo footprints between the murine c-myc P1 and P2 promoters.
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Cell death regulation during multistep lymphomagenesis
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Differentiation of F9 cells is independent of c-myc expression.
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Apoptosis Regulation by Raf, Bcl-2, and R-Ras
Troppmair, J., & Rapp, U. R. (1997) · Recent results in cancer research/Recent Results in Cancer Research · doi:10.1007/978-3-642-60393-8_17 · Cited by 10 · see citing works
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Glucocorticoid regulation of c-myc promoter utilization in P1798 T- lymphoma cells
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C-myc expression is down-regulated in mafosfamide-treated HL-60 cells undergoing apoptosis.
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Association with C-Myc: An Alternated Mechanism for c-Myc Function
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Deregulation of the c-myc and N-myc Genes in Transformed Cells
Dean, M. C., Cleveland, J. L., Kim, H.-Y., Campisi, J., Levine, R. A., Ihle, J. N., & Rapp, U. R. (1988) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-74006-0_29 · Cited by 4 · see citing works
Effects of 4-hydroxynonenal and N-acetyl-L-cysteine on Myc-induced apoptosis
Yıldız, D., Ercala, N., Frank, R. L., & Matthews, R. H. (1996) · Toxicology Letters · doi:10.1016/s0378-4274(96)03816-7 · Cited by 4 · see citing works
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Controls of Hair Follicle Cycling
Stenn, K. S., & Paus, R. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.1.449 · Cited by 1,520 · see citing works
Dang, C. V., O’Donnell, K. A., Zeller, K. I., Nguyen, T., Osthus, R. C., & Li, F. (2006) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2006.07.014 · Cited by 1,188 · see citing works
Mechanism and function of signal transduction by the Wnt/β-catenin and Wnt/Ca2+ pathways
Miller, J. R., Hocking, A. M., Brown, J. D., & Moon, R. T. (1999) · Oncogene · doi:10.1038/sj.onc.1203245 · Cited by 689 · see citing works
“However, c-myc cannot transform cells on its own and requires survival cues to prevent cells from undergoing apoptosis (reviewed in Steiner, 1996; Thompson, 1998).”
BackgroundVermeulen, K., Berneman, Z. N., & Bockstaele, D. R. V. (2003) · Cell Proliferation · doi:10.1046/j.1365-2184.2003.00267.x · Cited by 474 · see citing works
“This role was confirmed in different cell types under a wide variety of physiological conditions and both under- and overexpression of c-Myc can lead to cell death (reviewed in Conzen et al. 2000 and Thompson 1998).”
BackgroundThe myc Oncogene: arvelouslomplex
Oster, S. K., Ho, C. S. W., Soucie, E. L., & Penn, L. Z. (2002) · Advances in cancer research · doi:10.1016/s0065-230x(02)84004-0 · Cited by 459 · see citing works
c-Myc Is Required for Maintenance of Glioma Cancer Stem Cells
Wang, J., Wang, H., Li, Z., Wu, Q., Lathia, J. D., McLendon, R. E., Hjelmeland, A. B., & Rich, J. N. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003769 · Cited by 425 · see citing works
“Previous reports have demonstrated that c-Myc promotes apoptosis in cancer cell lines and various normal cell types, whereas downregulation of c-Myc also leads to apoptosis under certain circumstances [30,31,32,33].”
BackgroundAnalysis of C-MYC Function in Normal Cells via Conditional Gene-Targeted Mutation
de Alborán, I. M., O’Hagan, R. C., Gärtner, F., Malynn, B. A., Davidson, L., Rickert, R. C., Rajewsky, K., DePinho, R. A., & Alt, F. W. (2001) · Immunity · doi:10.1016/s1074-7613(01)00088-7 · Cited by 398 · see citing works
Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works
Recent insights into the mechanism of glucocorticosteroid-induced apoptosis
Distelhorst, C. (2002) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400969 · Cited by 287 · see citing works
Chen, Q. M., Juping, L. I. U., & MERRETT, J. B. (2000) · Biochemical Journal · doi:10.1042/0264-6021:3470543 · Cited by 280 · see citing works
NF-κB to the rescue: RELs, apoptosis and cellular transformation
Foo, S. Y., & Nolan, G. P. (1999) · Trends in Genetics · doi:10.1016/s0168-9525(99)01719-9 · Cited by 279 · see citing works
Repression of transcription of the p27Kip1 cyclin-dependent kinase inhibitor gene by c-Myc
Yang, W. E., Shen, J., Wu, M., Arsura, M., Fitzgerald, M. J., Suldan, Z., Kim, D. W., Hofmann, C. S., Pianetti, S., Romieu, R., et al. (2001) · Oncogene · doi:10.1038/sj.onc.1204245 · Cited by 277 · see citing works
“…has been demonstrated in an increasing number of cell types under various treatment conditions, including pre-B, erthyroleukemia, immature T cells, leukemia, lymphoid, melanoma and breast cancer cells (Besancon et al., 1998; KiharaNegishi et al., 1998; Wang et al., 1999; rev. in Thompson, 1998).”
BackgroundOrford, K. W., Orford, C. C., & Byers, S. W. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.146.4.855 · Cited by 276 · see citing works
“In fact, when overexpressed alone, c-myc markedly increases the susceptibility of cells to apoptosis (Desbarats et al., 1996; Steiner et al., 1996; Thompson, 1998).”
BackgroundHedgehog signaling in tissue homeostasis, cancers and targeted therapies
Jing, J., Wu, Z., Wang, J., Luo, G., Lin, H., Fan, Y., & Zhou, C. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01559-5 · Cited by 261 · see citing works
Miller, A. L., Webb, M. S., Copik, A. J., Wang, Y., Johnson, B. H., Kumar, P., & Thompson, E. B. (2005) · Molecular Endocrinology · doi:10.1210/me.2004-0528 · Cited by 241 · see citing works
Self-citationFunction and regulation of the transcription factors of the Myc/Max/Mad network
Lüscher, B. (2001) · Gene · doi:10.1016/s0378-1119(01)00697-7 · Cited by 238 · see citing works
“In addition Myc proteins can stimulate apoptosis, a finding that on first view does not seem to be compatible with the other functions mentioned above (Evan et al., 1992; Thompson, 1998; Prendergast, 1999).”
Apoptosis regulators and their role in tumorigenesis
Zörnig, M., Hueber, A., Baum, W., & Evan, G. I. (2001) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(01)00031-2 · Cited by 239 · see citing works
Lüscher, B., & Larsson, L. (1999) · Oncogene · doi:10.1038/sj.onc.1202750 · Cited by 212 · see citing works
“It appears that cells that express elevated levels of Myc are more susceptible to apoptosis induced by various stimuli (for review see Packham and Cleveland, 1995; Thompson, 1998).”
Backgroundc-Myc Phosphorylation Is Required for Cellular Response to Oxidative Stress
Benassi, B., Fanciulli, M., Fiorentino, F., Porrello, A., Chiorino, G., Loda, M. F., Zupi, G., & Biroccio, A. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.009 · Cited by 207 · see citing works
“However, the protective effect of cMyc reported here cannot be attributable to cell type, because it also occurs in MEF cells, where overexpression of c-Myc is reported to induce apoptosis (Hoffman and Liebermann, 1998; Thompson, 1998).”
Background“Large Cell/Anaplastic” Medulloblastomas: A Pediatric Oncology Group Study
Brown, H. G., Kepner, J. L., Perlman, E. J., Friedman, H. S., Strother, D. R., Duffner, P. K., Kun, L. E., Goldthwaite, P. T., & Burger, P. C. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.10.857 · Cited by 198 · see citing works
“The abundant apoptosis noted in the LC/A MBs would be in accord with the association between cmyc amplification and apoptosis (25).”
BackgroundPotential Role of Microsomal Prostaglandin E Synthase-1 in Tumorigenesis
Kamei, D., Murakami, M., Nakatani, Y., Ishikawa, Y., Ishii, T., & Kudo, I. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m213290200 · Cited by 198 · see citing works
CHEN, Q. M., LIU, J., & MERRETT, J. B. (2000) · Biochemical Journal · doi:10.1042/bj3470543 · Cited by 280 · see citing works
Comparative toxicity of oleic acid and linoleic acid on Jurkat cells
Cury‐Boaventura, M. F., Pompéia, C., & Curi, R. (2004) · Clinical Nutrition · doi:10.1016/j.clnu.2003.12.004 · Cited by 169 · see citing works
The c-MYCNHE III1: Function and Regulation
González, V., & Hurley, L. H. (2009) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.113006.094649 · Cited by 169 · see citing works
Activation of NF-kappaB/Rel occurs early during neoplastic transformation of mammary cells
Kim, D. W. (2000) · Carcinogenesis · doi:10.1093/carcin/21.5.871 · Cited by 160 · see citing works
The Connections Between Neural Crest Development and Neuroblastoma
Jiang, M., Stanke, J. J., & Lahti, J. M. (2011) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/b978-0-12-380916-2.00004-8 · Cited by 154 · see citing works
“Although the Myc gene was originally identified as an oncogene, it is involved in various cellular processes, including cell growth, proliferation, loss of differentiation, and apoptosis (Adhikary and Eilers, 2005; Pelengaris et al., 2002; Thompson, 1998).”
BackgroundInfluentialMyc Potentiates Apoptosis by Stimulating Bax Activity at the Mitochondria
Soucie, E. L., Annis, M. G., Sedivy, J. M., Filmus, J., Leber, B. F., Andrews, D. W., & Penn, L. Z. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.14.4725-4736.2001 · Cited by 148 · see citing works
“The role of Myc in potentiating apoptosis has led to several models for the mechanism of action (10, 17, 47, 55).”
BackgroundJin, Y. H., Yoo, K. J., Lee, Y. H., & Lee, S. K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001902200 · Cited by 147 · see citing works
Li, X., Zhang, Z., Gao, F., Ma, Y., Wei, D., Lu, Z., Chen, S., Wang, M., Wang, Y., Xu, K., et al. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c02619 · Cited by 145 · see citing works
Activation of p53 Tumor Suppressor by Hepatitis C Virus Core Protein
Lu, W. Y., Lo, S., Chen, M., Wu, K.-J., Fung, Y. K., & Ou, J. J. (1999) · Virology · doi:10.1006/viro.1999.9979 · Cited by 140 · see citing works
Mechanisms of glucocorticoid-induced apoptosis in hematologic malignancies: updates
Frankfurt, O., & Rosen, S. T. (2004) · Current Opinion in Oncology · doi:10.1097/01.cco.0000142072.22226.09 · Cited by 134 · see citing works
Induction of apoptosis by puerarin in colon cancer HT-29 cells
Yu, Z., & Li, W. (2005) · Cancer Letters · doi:10.1016/j.canlet.2005.06.022 · Cited by 133 · see citing works
Bernhard, D., Ausserlechner, M., Tonko, M., Löffler, M., Hartmann, B., Csordas, A., & Kofler, R. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.14.1991 · Cited by 136 · see citing works
“Previous studies have shown that butyrate treatment reduces c-myc mRNA levels (4, 10), and c-myc downregulation has been causally implicated in several death pathways (53).”
BackgroundExtra c-myc oncogene copies in high risk cutaneous malignant melanoma and melanoma metastases
Kraehn, G., Utikal, J. S., Udart, M., Greulich, K. M., Bezold, G., Kaskel, P., Leiter, U., & Peter, R. U. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2000.1535 · Cited by 128 · see citing works
“Myc family oncoproteins have been demonstrated to be sequencespecific transcription factors that are believed to regulate the expression of genes governing cellular growth, differentiation, and programmed cell death (Chin et al, 1996; Thompson, 1998).”
BackgroundFlozak, A. S., Lam, A. P., Russell, S., Jain, M., Peled, O. N., Sheppard, K. A., Beri, R., Mutlu, G. M., Budinger, G. R. S., & Gottardi, C. J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.070326 · Cited by 122 · see citing works
Kamemura, K., & Hart, G. W. (2003) · Progress in nucleic acid research and molecular biology · doi:10.1016/s0079-6603(03)01004-3 · Cited by 122 · see citing works
Differentially expressed genes in eutopic and ectopic endometrium of women with endometriosis
Meola, J., Silva, J. C. R. E., Dentillo, D. B., Silva, W. A., Veiga-Castelli, L. C., Bernardes, L. Â. D. S., Ferriani, R. A., de Paz, C. C. P., Giuliatti, S., & Martelli, L. R. (2009) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.12.058 · Cited by 120 · see citing works
Role of NF-κB and Myc Proteins in Apoptosis Induced by Hepatitis B Virus HBx Protein
Su, F., Theodosis, C. N., & Schneider, R. J. (2001) · Journal of Virology · doi:10.1128/jvi.75.1.215-225.2001 · Cited by 117 · see citing works
“In addition, Myc proteins can sensitize cells to killing by TNF-a by severalfold (56, 57, 102).”
BackgroundInvolvement of p38 in Apoptosis-associated Membrane Blebbing and Nuclear Condensation
Deschesnes, R. G., Huot, J., Valerie, K. C., & Landry, J. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.6.1569 · Cited by 117 · see citing works
“Many growth-promoting pathways can be either pro- or antiapoptotic, depending on the cellular context (Thompson, 1998; Joneson and Bar-Sagi, 1999).”
BackgroundJeay, S., Sonenshein, G. E., Postel-Vinay, M. C., Kelly, P. A., & Baixerás, E. (2002) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(02)00014-x · Cited by 116 · see citing works
Brunner, T. B. (2003) · Seminars in Immunology · doi:10.1016/s1044-5323(03)00035-6 · Cited by 110 · see citing works
“Paradoxically, c-Myc has also been implicated in regulation of apoptosis (reviewed in [92]).”
BackgroundAchanzar, W. E., Achanzar, K., Lewis, J. G., Webber, M. M., & Waalkes, M. P. (2000) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1999.8907 · Cited by 110 · see citing works
High Glucose Stimulates Early Response Gene c-Myc Expression in Rat Pancreatic β Cells
Jonas, J., Laybutt, D. R., Steil, G. M., Trivedi, N., Pertusa, J., de Casteele, M. V., Weir, G. C., & Henquin, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105020200 · Cited by 108 · see citing works
Tan, A., Bitterman, P. B., Sonenberg, N., Peterson, M., & Polunovsky, V. A. (2000) · Oncogene · doi:10.1038/sj.onc.1203446 · Cited by 106 · see citing works
“Cell cycle transit requires the function of c-Myc, a transcriptional regulatory phosphoprotein that has also been implicated in the activation of apoptosis (reviewed in Dang, 1999; Harrington et al., 1994; Thompson, 1998).”
BackgroundYang, B., Cao, L., Liu, B., McCaig, C., & Pu, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060861 · Cited by 98 · see citing works
“Butyrate also increases the differentiation of human LIM2537 colon cancer cells, decreases GSK-3b activity and increases levels of both membrane-bound and Apc/axin/ GSK-3b complex-associated pools of b-catenin [39].”
BackgroundSimultaneous expression of different immunogenic antigens in acute myeloid leukemia
Greiner, J., Ringhoffer, M., Simikopinko, O., Szmaragowska, A., Hübsch, S., Maurer, U., Bergmann, L., & Schmitt, M. W. (2000) · Experimental Hematology · doi:10.1016/s0301-472x(00)00550-6 · Cited by 97 · see citing works
“The characterized antigen MAZ regulates expression of c-myc [26,27], a proto-oncogene involved in the oncogenesis of Burkitt lymphoma [28].”
BackgroundMethodZhu, Q., Zhang, C., Qu, T., Lu, X., He, X., Li, W., Yin, D., Han, L., Guo, R., & Zhang, E. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-1289 · Cited by 95 · see citing works
In Vivo Study of AT1and AT2Angiotensin Receptors in Apoptosis in Rat Blood Vessels
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“(22) Taken together, our findings of increased expres sion of Fas and c-Myc and reduced expression of bcl-2 in ICAM-1(1) cells suggest that the cells might be apoptotic at least partially mediated by Fas.”
BackgroundControl of cellular senescence by CPEBPreprint
Groisman, I., Ivshina, M. P., Marin, V., Kennedy, N. J., Davis, R. J., & Richter, J. D. (2006) · Genes & Development · doi:10.1101/gad.1438906 · Cited by 94 · see citing works
“1989), but can induce apoptosis as well (Thompson 1998).”
BackgroundBustin, S. A., Li, S.-R., & Dorudi, S. (2001) · DNA and Cell Biology · doi:10.1089/10445490152122442 · Cited by 92 · see citing works
Mazure, N. M., Chauvet, C., Bois-Joyeux, B., Bernard, M.-A., Nacer-Chérif, H., & Danan, J.-L. (2002) · PubMed · Cited by 90 · see citing works
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“In the absence of survival factors, c-myc is a potentiator of apoptosis, whereas in other instances, such as glucocorticoid or nitric oxide–driven apoptosis, c-Myc is required to protect cells from death (13).”
BackgroundYang, X., Liu, D., Murray, T. J., Mitchell, G. C., Hestermann, E. V., Karchner, S. I., Merson, R. R., Hahn, M. E., & Sherr, D. H. (2005) · Oncogene · doi:10.1038/sj.onc.1208938 · Cited by 86 · see citing works
“…directly transcription of c-myc, an important oncogene that can regulate cell growth (Pelengaris and Khan, 2003) and apoptosis (Wu et al., 1996; Thompson, 1998; Ryu et al., 2003) and which is dysregulated in many tumor types including breast cancers (Escot et al., 1986; Leder et al., 1986;…”
BackgroundZhao, Q., Assimopoulou, A. N., Klauck, S. M., Damianakos, H., Chinou, İ., Kretschmer, N., Rı́os, J.-L., Papageorgiou, V. P., Bauer, R., & Efferth, T. (2015) · Oncotarget · doi:10.18632/oncotarget.5380 · Cited by 85 · see citing works
“Both reduction and overexpression of c-MYC can lead to apoptosis [45, 46].”
Backgroundc-Myc Is Necessary for DNA Damage-Induced Apoptosis in the G2 Phase of the Cell Cycle
Adachi, S., Obaya, Á. J., Han, Z., RAMOS‐DeSIMONE, N., Wyche, J. H., & Sedivy, J. M. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.15.4929-4937.2001 · Cited by 85 · see citing works
“For example, in a variety of transformed cell types c-myc antisense oligonucleotides cause growth inhibition, which in some (but not all) cases is associated with the onset of apoptosis (51).”
BackgroundOncogene Activation in Pituitary Tumors
Yu, R., & Melmed, S. K. (2001) · Brain Pathology · doi:10.1111/j.1750-3639.2001.tb00403.x · Cited by 84 · see citing works
“For example, myc or E1A overexpression result in cell apoptosis (10, 19, 63, 69, 70, 72).”
BackgroundInfluentialWu, X., Liu, L., Zheng, Q., Hao, H., Ye, H., Li, P., & Yang, H. Q. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.03.021 · Cited by 84 · see citing works
Pancreatic β cells control glucose homeostasis via the secretion of exosomal miR‐29 family
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“FFAs triggered a sharp reduction in c-Myc (Ayala-Torres et al., 1997; Thompson, 1998), which can bind bothmiR-29b-1/a andmiR-29b-2/c in the vicinity of the transcription start site and negatively regulate miR-29 expression (Kriegel et al., 2012).”
BackgroundCurrent status of the molecular genetics of human prostatic adenocarcinomas
Karan, D., Lin, M., Johansson, S. L., & Batra, S. K. (2002) · International Journal of Cancer · doi:10.1002/ijc.10813 · Cited by 80 · see citing works
Reversible lymphomagenesis in conditionally c‐MYC expressing mice
Marinković, D., Marinković, T., Mahr, B., Heß, J., & Wirth, T. C. (2004) · International Journal of Cancer · doi:10.1002/ijc.20099 · Cited by 79 · see citing works
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“In some leukemic and lymphoid cell lines c-myc levels must decline for glucocorticoid, dexamethasone induced apoptosis (Thompson, 1998).”
BackgroundMolecular Pathways in Prostate Cancer
Mazaris, E. M., & Tsiotras, A. (2013) · Nephro-Urology Monthly · doi:10.5812/numonthly.9430 · Cited by 75 · see citing works
“It encodes the c-MYC protein, which promotes cell proliferation and transformation (5, 89).”
BackgroundThe role of constitutive NF-κB activity in PC-3 human prostate cancer cell invasive behavior
Lindholm, P. F., Bub, J. D., Kaul, S., Shidham, V. B., & Kajdacsy‐Balla, A. (2000) · Clinical & Experimental Metastasis · doi:10.1023/a:1011845725394 · Cited by 75 · see citing works
“NF-κB may exert its anti-apoptotic effects by upregulation of TRAFs, bcl-2, c-myc, p53 and inhibition of apoptosis [21, 22].”
BackgroundProteasomes in apoptosis: villains or guardians?
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Role of programmed cell death in development
Ranganath, R. M., & Nagashree, N. R. (2001) · International review of cytology · doi:10.1016/s0074-7696(01)02005-8 · Cited by 71 · see citing works
Hayashi, T., & Faustman, D. L. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.7.5238 · Cited by 70 · see citing works
Physical and functional interaction between HCV core protein and the different p73 isoforms
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Venditti, M., Iwasiow, B. M., Orr, F. W., & Shiu, R. P. C. (2002) · International Journal of Cancer · doi:10.1002/ijc.10269 · Cited by 69 · see citing works
New Wnt/β‐Catenin Signaling Inhibitors Isolated from Eleutherine palmifolia
Li, X., Ohtsuki, T., Koyano, T., Kowithayakorn, T., & Ishibashi, M. (2008) · Chemistry - An Asian Journal · doi:10.1002/asia.200800354 · Cited by 68 · see citing works
Dicer-Dependent MicroRNAs Control Maturation, Function, and Maintenance of Langerhans Cells In Vivo
Kuipers, H., Schnorfeil, F. M., Fehling, H. J., Bartels, H., & Brocker, T. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903912 · Cited by 66 · see citing works
DIMAS, K. S., Demetzos, C., Vaos, V., Ioannidis, P., & Trangas, T. T. (2001) · Leukemia Research · doi:10.1016/s0145-2126(00)00150-8 · Cited by 67 · see citing works
Regulation of the Resident Chromosomal Copy of c-myc by c-Myb Is Involved in Myeloid Leukemogenesis
Schmidt, M., Nazarov, V., Stevens, L. M., Watson, R., & Wolff, L. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.6.1970-1981.2000 · Cited by 67 · see citing works
“To further evaluate downstream effects of deregulated c-myc expression due to activation of MybEnER, we examined the influence of the dominant negative protein on another target gene of cMyc, ODC.”
BackgroundInfluentialHideshima, T., Cottini, F., Ohguchi, H., Jakubı́ková, J., Görgün, G., Mimura, N., Tai, Y., Munshi, N. C., Richardson, P. G. G., & Anderson, K. C. (2015) · Blood Cancer Journal · doi:10.1038/bcj.2015.38 · Cited by 65 · see citing works
Ma, G., Yang, C., Qu, Y., Wei, H., Zhang, T., & Zhang, N. (2007) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2007.02.006 · Cited by 64 · see citing works
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Biroccio, A., Benassi, B., Fiorentino, F. P., & Zupi, G. (2004) · Neoplasia · doi:10.1593/neo.03370 · Cited by 64 · see citing works
“For example, c-myc antisense or dominant-defective causes apoptosis in a variety of transformed cell types [3], whereas c-Myc expression can sensitize cells to a wide range of different stimuli such as low serum conditions [4], hypoxia [5], and deprivation of specific growth factors [6] [7].”
BackgroundHotti, A., Järvinen, K., Siivola, P., & Hölttä, E. (2000) · Oncogene · doi:10.1038/sj.onc.1203567 · Cited by 63 · see citing works
“Also, it is not clear whether the tumour suppressor p53, a transcriptional target for cMyc, is needed for apoptosis induced by c-Myc (Lotem and Sachs, 1995; Shim et al., 1998; Wagner et al., 1994; Zindy et al., 1998; reviewed in Prendergast, 1999; Thompson, 1998).”
BackgroundChrzan, P., Skokowski, J., Karmoliński, A., & Pawełczyk, T. (2001) · Clinical Biochemistry · doi:10.1016/s0009-9120(01)00260-0 · Cited by 63 · see citing works
Comparative toxicity of oleic acid and linoleic acid on Raji cells
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c-Myc antagonizes the effect of p53 on apoptosis and p21WAF1 transactivation in K562 leukemia cells
Ceballos, E., Delgado, M. D., Gutierrez, P., Richard, C., Müller, D., Eilers, M., Ehinger, M., Gullberg, U., & León, J. (2000) · Oncogene · doi:10.1038/sj.onc.1203541 · Cited by 61 · see citing works
“…growth conditions, e.g. deprivation of growth factors or hypoxia (for recent reviews see Ho man and Lieberman, 1998; Hueber and Evan, 1998; Thompson, 1998). c-Mycmediated apoptosis requires wild-type p53 in ®broblasts (Hermeking and Eick, 1994; Wagner et al., 1994; Rupnow et al., 1998),…”
BackgroundShi, Y., Hasebe, T., Fu, L., Fujimoto, K., & Ishizuya‐Oka, A. (2011) · Cell & Bioscience · doi:10.1186/2045-3701-1-30 · Cited by 60 · see citing works
c-myc antisense oligonucleotide treatment ameliorates murine ARPKD
Ricker, J. L., Mata, J. E., Iversen, P. L., & Gattone, V. H. (2002) · Kidney International · doi:10.1046/j.1523-1755.2002.0610s1125.x · Cited by 57 · see citing works
“DISCUSSION The c-myc gene, located on mouse chromosome 15, encodes 64 to 67 kD proteins containing domains that function in nuclear localization, non-specific and sequence-specific DNA binding, and oligomerizatio”
BackgroundWang, H., Ye, Y., Pan, S.-Y., Zhu, G., Li, Y., Fong, D. W. F., & Yu, Z. (2010) · Phytomedicine · doi:10.1016/j.phymed.2010.06.011 · Cited by 56 · see citing works
Fatal Acute Lymphoblastic Leukemia in Mice Transgenic for B Cell-Restricted bcl-xL and c- myc
Swanson, P. J., Kuslak, S. L., Wei, F., Tze, L. E., Gaffney, P. M., Selby, S. A., Hippen, K. L., Núñez, G., Sidman, C. L., & Behrens, T. W. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.11.6684 · Cited by 55 · see citing works
“Dysregulated expression of Myc causes cell cycle progression and proliferation, and, in addition, also induces apoptotic cell death (9).”
BackgroundMediterranean Mussel Gene Expression Profile Induced by Okadaic Acid Exposure
Manfrin, C., Dreos, R., Battistella, S., Beran, A. R., Gerdol, M., Varotto, L., Lanfranchi, G., Venier, P., & Pallavicini, A. (2010) · Environmental Science & Technology · doi:10.1021/es102213f · Cited by 55 · see citing works
Quéva, C., McArthur, G. A., Iritani, B. M., & Eisenman, R. N. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.3.703-712.2001 · Cited by 55 · see citing works
“Because mad3 and c-Myc were coexpressed in the thymus (44), where Myc has been shown elsewhere to influence apoptosis in T lymphocytes (22, 42, 53, 57), we examined the response of mad3 and mad3 T cells to apoptotic stimuli.”
BackgroundInvolvement of Nuclear Factor κB in c-Myc Induction by Tubulin Polymerization Inhibitors
Bourgarel‐Rey, V., Vallée, S., Rimet, O., Champion, S., Braguer, D., Desobry, A., Briand, C. M., & Barra, Y. (2001) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)12576-x · Cited by 54 · see citing works
Huang, Y., Wu, J. Y., Zhang, Y., & Wu, M. X. (2002) · Oncogene · doi:10.1038/sj.onc.1205854 · Cited by 51 · see citing works
“…indicating an involvement of coactivators, other than p300 or CBP, which remains to be investigated. c-Myc and p53 are well documented to be functionally related in several different systems (Bates and Vousden, 1999; Prendergast, 1999; Hermeking and Eick, 1994; Sala et al., 1996; Thompson, 1998).”
BackgroundVariable functions of bcl-2 in mediating bioreactor stress- induced apoptosis in hybridoma cells
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Effect of inositol hexaphosphate (IP6) on human normal and leukaemic haematopoietic cells
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“Transcription factors that promote cell proliferation, including c-myc and HPTPCAAX1 (Diamond et al, 1996; Thompson, 1998), were downregulated upon incubation in the presence of IP6.”
BackgroundTargeting Regulated Chondrocyte Death in Osteoarthritis Therapy.
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Glucocorticoid resistance in childhood leukaemia: mechanisms and modulation
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“Studies generally focused on the typical apoptosis genes (Thulasi et al, 1993; Thompson, 1998; Kofler, 2000), or tried to identify 2003 Blackwell Publishing Ltd, British Journal of Haematology 120: 919–929 candidate genes by ‘gene search approaches’ (Briehl et al, 1990; Baughman et al, 1991).”
BackgroundRegulation and clinical potential of telomerase reverse transcriptase (TERT/hTERT) in breast cancer
Yang, R., Han, Y., Guan, X., Hong, Y., Meng, J., Ding, S., Qian, L., & Yi, W. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01244-8 · Cited by 49 · see citing works
“The N-terminal transactivation domain of c-MYC recognizes E-box motifs (5’-CAC GTG -3’ sequence) on DNA, enabling c-MYC/MAX heterodimers to bind to regulatory sequences like promoters and regulate target gene transcription [68, 69].”
BackgroundThe MYC dualism in growth and death
Fuhrmann, G., Rosenberger, G., Grusch, M., Klein, N., Hofmann, J. F.-X., & Krupitza, G. (1999) · Mutation Research/Reviews in Mutation Research · doi:10.1016/s1383-5742(99)00084-8 · Cited by 48 · see citing works
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- Authors
- Thompson, E. B.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Corresponding author
- Thompson, E. Brad
- ORCID
- Thompson, E. Brad
- Venue
- Annual Review of Physiology
- Publisher
- Annual Reviews
- Published
- 1998-10
- Volume
- 60
- Issue
- 1
- Pages
- 575-600
- ISSN
- 0066-4278 (ISSN-L)
- 1545-1585
- OpenAlex
- W2104373533
- Cited by
- 328
- References
- 159
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 24 · 2023: 31 · 2022: 17 · 2021: 10 · 2020: 6 · 2019: 2 · 2018: 3 · 2017: 6 · 2015: 10 · 2014: 3 · 2013: 6 · 2012: 3
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- c-Myc, c-myc proto-oncogene, apoptosis, transcription factor regulation, gene expression regulation, gene repression, cell growth regulation, transcriptional regulation
- MeSH terms
- Proto-Oncogene Mas, Animals, Humans, Genes, myc, Proto-Oncogene Proteins c-myc, Apoptosis
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