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Isoform-Directed Control of c-Myc Functions: Understanding the Balance from Proliferation to Growth Arrest

. 2023 Dec 15 ; 24 (24) : . [epub] 20231215

Language English Country Switzerland Media electronic

Document type Journal Article, Review

Grant support
LM2018133 Ministry of Youth, School, Education and Sport of the Czech Republic
LX22NPO5102 Ministry of Youth, School, Education and Sport of the Czech Republic

The transcription factor c-Myc, a key regulator of cellular processes, has long been associated with roles in cell proliferation and apoptosis. This review analyses the multiple functions of c-Myc by examining the different c-Myc isoforms in detail. The impact of different c-Myc isoforms, in particular p64 and p67, on fundamental biological processes remains controversial. It is necessary to investigate the different isoforms in the context of proto-oncogenesis. The current knowledge base suggests that neoplastic lesions may possess the means for self-destruction via increased c-Myc activity. This review presents the most relevant information on the c-Myc locus and focuses on a number of isoforms, including p64 and p67. This compilation provides a basis for the development of therapeutic approaches that target the potent growth arresting and pro-apoptotic functions of c-Myc. This information can then be used to develop targeted interventions against specific isoforms with the aim of shifting the oncogenic effects of c-Myc from pro-proliferative to pro-apoptotic. The research summarised in this review can deepen our understanding of how c-Myc activity contributes to different cellular responses, which will be crucial in developing effective therapeutic strategies; for example, isoform-specific approaches may allow for precise modulation of c-Myc function.

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Amati B., Frank S.R., Donjerkovic D., Taubert S. Function of the C-Myc Oncoprotein in Chromatin Remodeling and Transcription. Biochim. Biophys. Acta. 2001;1471:M135–M145. doi: 10.1016/S0304-419X(01)00020-8. PubMed DOI

Dang C.V., O’Donnell K.A., Zeller K.I., Nguyen T., Osthus R.C., Li F. The C-Myc Target Gene Network. Semin. Cancer Biol. 2006;16:253–264. doi: 10.1016/j.semcancer.2006.07.014. PubMed DOI

Yang W., Shen J., Wu M., Arsura M., FitzGerald M., Suldan Z., Kim D.W., Hofmann C.S., Pianetti S., Romieu-Mourez R., et al. Repression of Transcription of the P27(Kip1) Cyclin-Dependent Kinase Inhibitor Gene by c-Myc. Oncogene. 2001;20:1688–1702. doi: 10.1038/sj.onc.1204245. PubMed DOI

Xiao L., Wang Y., Liang W., Liu L., Pan N., Deng H., Li L., Zou C., Chan F.L., Zhou Y. LRH-1 Drives Hepatocellular Carcinoma Partially through Induction of c-Myc and Cyclin E1, and Suppression of P21. Cancer Manag. Res. 2018;10:2389–2400. doi: 10.2147/CMAR.S162887. PubMed DOI PMC

Zhang J., Song N., Zang D., Yu J., Li J., Di W., Guo R., Zhao W., Wang H. C-Myc Promotes Tumor Proliferation and Anti-apoptosis by Repressing P21 in Rhabdomyosarcomas. Mol. Med. Rep. 2017;16:4089–4094. doi: 10.3892/mmr.2017.7101. PubMed DOI

Gruszka R., Zakrzewski K., Liberski P.P., Zakrzewska M. mRNA and miRNA Expression Analyses of the MYC/E2F/miR-17-92 Network in the Most Common Pediatric Brain Tumors. Int. J. Mol. Sci. 2021;22:543. doi: 10.3390/ijms22020543. PubMed DOI PMC

Bretones G., Delgado M.D., León J. Myc and Cell Cycle Control. Biochim. Biophys. Acta. 2015;1849:506–516. doi: 10.1016/j.bbagrm.2014.03.013. PubMed DOI

Spencer C.A., Groudine M. Control of C-Myc Regulation in Normal and Neoplastic Cells. Adv. Cancer Res. 1991;56:1–48. doi: 10.1016/s0065-230x(08)60476-5. PubMed DOI

Dhanasekaran R., Deutzmann A., Mahauad-Fernandez W.D., Hansen A.S., Gouw A.M., Felsher D.W. The MYC Oncogene—The Grand Orchestrator of Cancer Growth and Immune Evasion. Nat. Rev. Clin. Oncol. 2022;19:23–36. doi: 10.1038/s41571-021-00549-2. PubMed DOI PMC

Gao F.Y., Li X.T., Xu K., Wang R.T., Guan X.X. C-MYC Mediates the Crosstalk between Breast Cancer Cells and Tumor Microenvironment. Cell Commun. Signal. 2023;21:28. doi: 10.1186/s12964-023-01043-1. PubMed DOI PMC

Chanvorachote P., Sriratanasak N., Nonpanya N. C-Myc Contributes to Malignancy of Lung Cancer: A Potential Anticancer Drug Target. Anticancer Res. 2020;40:609–618. doi: 10.21873/anticanres.13990. PubMed DOI

Di Y., Jing X., Hu K., Wen X., Ye L., Zhang X., Qin J., Ye J., Lin R., Wang Z., et al. The C-MYC-WDR43 Signalling Axis Promotes Chemoresistance and Tumour Growth in Colorectal Cancer by Inhibiting P53 Activity. Drug Resist. Updat. 2023;66:100909. doi: 10.1016/j.drup.2022.100909. PubMed DOI

Evan G.I., Wyllie A.H., Gilbert C.S., Littlewood T.D., Land H., Brooks M., Waters C.M., Penn L.Z., Hancock D.C. Induction of Apoptosis in Fibroblasts by C-Myc Protein. Cell. 1992;69:119–128. doi: 10.1016/0092-8674(92)90123-T. PubMed DOI

McMahon S.B. MYC and the Control of Apoptosis. Cold Spring Harb. Perspect. Med. 2014;4:a014407. doi: 10.1101/cshperspect.a014407. PubMed DOI PMC

Kotulova J., Lonova K., Kubickova A., Vrbkova J., Kourilova P., Hajduch M., Dzubak P. 2-Cl-IB-MECA Regulates the Proliferative and Drug Resistance Pathways, and Facilitates Chemosensitivity in Pancreatic and Liver Cancer Cell Lines. Int. J. Mol. Med. 2022;49:31. doi: 10.3892/ijmm.2022.5086. PubMed DOI PMC

Yoshida G.J. Emerging Roles of Myc in Stem Cell Biology and Novel Tumor Therapies. J. Exp. Clin. Cancer Res. 2018;37:173. doi: 10.1186/s13046-018-0835-y. PubMed DOI PMC

Macečková Z., Kubíčková A., Sanctis J.B.D., Hajdúch M. Effect of Glucocorticosteroids in Diamond-Blackfan Anaemia: Maybe Not as Elusive as It Seems. Int. J. Mol. Sci. 2022;23:1886. doi: 10.3390/ijms23031886. PubMed DOI PMC

Kubickova A., Maceckova Z., Vojta P., Ondra M., Volejnikova J., Koralkova P., Jungova A., Jahoda O., Mojzikova R., Hadacova I., et al. Missense Mutation in RPS7 Causes Diamond-Blackfan Anemia via Alteration of Erythrocyte Metabolism, Protein Translation and Induction of Ribosomal Stress. Blood Cells Mol. Dis. 2022;97:102690. doi: 10.1016/j.bcmd.2022.102690. PubMed DOI

Okita K., Ichisaka T., Yamanaka S. Generation of Germline-Competent Induced Pluripotent Stem Cells. Nature. 2007;448:313–317. doi: 10.1038/nature05934. PubMed DOI

Llombart V., Mansour M.R. Therapeutic Targeting of “Undruggable” MYC. EBioMedicine. 2022;75:103756. doi: 10.1016/j.ebiom.2021.103756. PubMed DOI PMC

Cole M.D. The Myc Oncogene: Its Role in Transformation and Differentiation. Annu. Rev. Genet. 1986;20:361–384. doi: 10.1146/annurev.ge.20.120186.002045. PubMed DOI

Henriksson M., Lüscher B. Proteins of the Myc Network: Essential Regulators of Cell Growth and Differentiation. Adv. Cancer Res. 1996;68:109–182. doi: 10.1016/s0065-230x(08)60353-x. PubMed DOI

Lüscher B., Eisenman R.N. New Light on Myc and Myb. Part I. Myc. Genes Dev. 1990;4:2025–2035. doi: 10.1101/gad.4.12a.2025. PubMed DOI

Ryan K.M., Birnie G.D. Myc Oncogenes: The Enigmatic Family. Pt 3Biochem. J. 1996;314:713–721. doi: 10.1042/bj3140713. PubMed DOI PMC

Hann S.R., Eisenman R.N. Proteins Encoded by the Human C-Myc Oncogene: Differential Expression in Neoplastic Cells. Mol. Cell. Biol. 1984;4:2486–2497. doi: 10.1128/mcb.4.11.2486-2497.1984. PubMed DOI PMC

Ramsay G., Evan G.I., Bishop J.M. The Protein Encoded by the Human Proto-Oncogene c-Myc. Proc. Natl. Acad. Sci. USA. 1984;81:7742–7746. doi: 10.1073/pnas.81.24.7742. PubMed DOI PMC

Blackwood E.M., Eisenman R.N. Max: A Helix-Loop-Helix Zipper Protein That Forms a Sequence-Specific DNA-Binding Complex with Myc. Science. 1991;251:1211–1217. doi: 10.1126/science.2006410. PubMed DOI

Blackwell T.K., Kretzner L., Blackwood E.M., Eisenman R.N., Weintraub H. Sequence-Specific DNA Binding by the c-Myc Protein. Science. 1990;250:1149–1151. doi: 10.1126/science.2251503. PubMed DOI

Prendergast G.C., Ziff E.B. Methylation-Sensitive Sequence-Specific DNA Binding by the c-Myc Basic Region. Science. 1991;251:186–189. doi: 10.1126/science.1987636. PubMed DOI

Amati B., Brooks M.W., Levy N., Littlewood T.D., Evan G.I., Land H. Oncogenic Activity of the C-Myc Protein Requires Dimerization with Max. Cell. 1993;72:233–245. doi: 10.1016/0092-8674(93)90663-B. PubMed DOI

Amin C., Wagner A.J., Hay N. Sequence-Specific Transcriptional Activation by Myc and Repression by Max. Mol. Cell. Biol. 1993;13:383–390. doi: 10.1128/mcb.13.1.383-390.1993. PubMed DOI PMC

Kretzner L., Blackwood E.M., Eisenman R.N. Myc and Max Proteins Possess Distinct Transcriptional Activities. Nature. 1992;359:426–429. doi: 10.1038/359426a0. PubMed DOI

Kato G.J., Barrett J., Villa-Garcia M., Dang C.V. An Amino-Terminal c-Myc Domain Required for Neoplastic Transformation Activates Transcription. Mol. Cell. Biol. 1990;10:5914–5920. doi: 10.1128/mcb.10.11.5914-5920.1990. PubMed DOI PMC

Gu W., Bhatia K., Magrath I.T., Dang C.V., Dalla-Favera R. Binding and Suppression of the Myc Transcriptional Activation Domain by P107. Science. 1994;264:251–254. doi: 10.1126/science.8146655. PubMed DOI

Maheswaran S., Lee H., Sonenshein G.E. Intracellular Association of the Protein Product of the C-Myc Oncogene with the TATA-Binding Protein. Mol. Cell. Biol. 1994;14:1147–1152. doi: 10.1128/mcb.14.2.1147-1152.1994. PubMed DOI PMC

Grandori C., Mac J., Siëbelt F., Ayer D.E., Eisenman R.N. Myc-Max Heterodimers Activate a DEAD Box Gene and Interact with Multiple E Box-Related Sites in Vivo. EMBO J. 1996;15:4344–4357. doi: 10.1002/j.1460-2075.1996.tb00808.x. PubMed DOI PMC

Boyd K.E., Farnham P.J. Myc versus USF: Discrimination at the Cad Gene Is Determined by Core Promoter Elements. Mol. Cell. Biol. 1997;17:2529–2537. doi: 10.1128/MCB.17.5.2529. PubMed DOI PMC

O’Connell B.C., Cheung A.F., Simkevich C.P., Tam W., Ren X., Mateyak M.K., Sedivy J.M. A Large Scale Genetic Analysis of C-Myc-Regulated Gene Expression Patterns. J. Biol. Chem. 2003;278:12563–12573. doi: 10.1074/jbc.M210462200. PubMed DOI

Hölzel M., Kohlhuber F., Schlosser I., Hölzel D., Lüscher B., Eick D. Myc/Max/Mad Regulate the Frequency but Not the Duration of Productive Cell Cycles. EMBO Rep. 2001;2:1125–1132. doi: 10.1093/embo-reports/kve251. PubMed DOI PMC

Choi H., Jackson N.L., Shaw D.R., Emanuel P.D., Liu Y.L., Tousson A., Meng Z., Blume S.W. Mrtl-A Translation/Localization Regulatory Protein Encoded within the Human c-Myc Locus and Distributed throughout the Endoplasmic and Nucleoplasmic Reticular Network. J. Cell Biochem. 2008;105:1092–1108. doi: 10.1002/jcb.21909. PubMed DOI PMC

Arabi A., Wu S., Ridderstråle K., Bierhoff H., Shiue C., Fatyol K., Fahlén S., Hydbring P., Söderberg O., Grummt I., et al. C-Myc Associates with Ribosomal DNA and Activates RNA Polymerase I Transcription. Nat. Cell Biol. 2005;7:303–310. doi: 10.1038/ncb1225. PubMed DOI

Grandori C., Gomez-Roman N., Felton-Edkins Z.A., Ngouenet C., Galloway D.A., Eisenman R.N., White R.J. C-Myc Binds to Human Ribosomal DNA and Stimulates Transcription of rRNA Genes by RNA Polymerase I. Nat. Cell Biol. 2005;7:311–318. doi: 10.1038/ncb1224. PubMed DOI

Gomez-Roman N., Grandori C., Eisenman R.N., White R.J. Direct Activation of RNA Polymerase III Transcription by C-Myc. Nature. 2003;421:290–294. doi: 10.1038/nature01327. PubMed DOI

Frye M., Gardner C., Li E.R., Arnold I., Watt F.M. Evidence That Myc Activation Depletes the Epidermal Stem Cell Compartment by Modulating Adhesive Interactions with the Local Microenvironment. Development. 2003;130:2793–2808. doi: 10.1242/dev.00462. PubMed DOI

Shiio Y., Donohoe S., Yi E.C., Goodlett D.R., Aebersold R., Eisenman R.N. Quantitative Proteomic Analysis of Myc Oncoprotein Function. EMBO J. 2002;21:5088–5096. doi: 10.1093/emboj/cdf525. PubMed DOI PMC

Mateyak M.K., Obaya A.J., Adachi S., Sedivy J.M. Phenotypes of C-Myc-Deficient Rat Fibroblasts Isolated by Targeted Homologous Recombination. Cell Growth Differ. 1997;8:1039–1048. PubMed

Sakamuro D., Eviner V., Elliott K.J., Showe L., White E., Prendergast G.C. C-Myc Induces Apoptosis in Epithelial Cells by Both P53-Dependent and P53-Independent Mechanisms. Oncogene. 1995;11:2411–2418. PubMed

Blume S.W., Miller D.M., Guarcello V., Shrestha K., Meng Z., Snyder R.C., Grizzle W.E., Ruppert J.M., Gartland G.L., Stockard C.R., et al. Inhibition of Tumorigenicity by the 5′-Untranslated RNA of the Human c-Myc P0 Transcript. Exp. Cell Res. 2003;288:131–142. doi: 10.1016/S0014-4827(03)00182-4. PubMed DOI

Marin M.C., Hsu B., Stephens L.C., Brisbay S., McDonnell T.J. The Functional Basis of C-Myc and Bcl-2 Complementation during Multistep Lymphomagenesis in Vivo. Exp. Cell Res. 1995;217:240–247. doi: 10.1006/excr.1995.1083. PubMed DOI

Zindy F., Eischen C.M., Randle D.H., Kamijo T., Cleveland J.L., Sherr C.J., Roussel M.F. Myc Signaling via the ARF Tumor Suppressor Regulates P53-Dependent Apoptosis and Immortalization. Genes Dev. 1998;12:2424–2433. doi: 10.1101/gad.12.15.2424. PubMed DOI PMC

Klein G. Dysregulation of Lymphocyte Proliferation by Chromosomal Translocations and Sequential Genetic Changes. Bioessays. 2000;22:414–422. doi: 10.1002/(SICI)1521-1878(200005)22:5<414::AID-BIES3>3.0.CO;2-5. PubMed DOI

Ge K., Duhadaway J., Sakamuro D., Wechsler-Reya R., Reynolds C., Prendergast G.C. Losses of the Tumor Suppressor BIN1 in Breast Carcinoma Are Frequent and Reflect Deficits in Programmed Cell Death Capacity. Int. J. Cancer. 2000;85:376–383. PubMed

Martin S.J., Green D.R. Protease Activation during Apoptosis: Death by a Thousand Cuts? Cell. 1995;82:349–352. doi: 10.1016/0092-8674(95)90422-0. PubMed DOI

Fearnhead H.O., McCurrach M.E., O’Neill J., Zhang K., Lowe S.W., Lazebnik Y.A. Oncogene-Dependent Apoptosis in Extracts from Drug-Resistant Cells. Genes Dev. 1997;11:1266–1276. doi: 10.1101/gad.11.10.1266. PubMed DOI

Armstrong D.K., Isaacs J.T., Ottaviano Y.L., Davidson N.E. Programmed Cell Death in an Estrogen-Independent Human Breast Cancer Cell Line, MDA-MB-468. Cancer Res. 1992;52:3418–3424. PubMed

Fukasawa K., Wiener F., Vande Woude G.F., Mai S. Genomic Instability and Apoptosis Are Frequent in P53 Deficient Young Mice. Oncogene. 1997;15:1295–1302. doi: 10.1038/sj.onc.1201482. PubMed DOI

Quelle D.E., Zindy F., Ashmun R.A., Sherr C.J. Alternative Reading Frames of the INK4a Tumor Suppressor Gene Encode Two Unrelated Proteins Capable of Inducing Cell Cycle Arrest. Cell. 1995;83:993–1000. doi: 10.1016/0092-8674(95)90214-7. PubMed DOI

Sherr C.J. Tumor Surveillance via the ARF-P53 Pathway. Genes Dev. 1998;12:2984–2991. doi: 10.1101/gad.12.19.2984. PubMed DOI

Watt R., Nishikura K., Sorrentino J., ar-Rushdi A., Croce C.M., Rovera G. The Structure and Nucleotide Sequence of the 5′ End of the Human c-Myc Oncogene. Proc. Natl. Acad. Sci. USA. 1983;80:6307–6311. doi: 10.1073/pnas.80.20.6307. PubMed DOI PMC

Bentley D.L., Groudine M. Novel Promoter Upstream of the Human C-Myc Gene and Regulation of c-Myc Expression in B-Cell Lymphomas. Mol. Cell. Biol. 1986;6:3481–3489. doi: 10.1128/mcb.6.10.3481-3489.1986. PubMed DOI PMC

Ray D., Robert-Lézénès J. Coexistence of a C-Myc mRNA Initiated in Intron 1 with the Normal c-Myc mRNA and Similar Regulation of Both Transcripts in Mammalian Cells. Oncogene Res. 1989;5:73–78. PubMed

Nanbru C., Prats A.C., Droogmans L., Defrance P., Huez G., Kruys V. Translation of the Human C-Myc P0 Tricistronic mRNA Involves Two Independent Internal Ribosome Entry Sites. Oncogene. 2001;20:4270–4280. doi: 10.1038/sj.onc.1204548. PubMed DOI

Hann S.R., King M.W., Bentley D.L., Anderson C.W., Eisenman R.N. A Non-AUG Translational Initiation in c-Myc Exon 1 Generates an N-Terminally Distinct Protein Whose Synthesis Is Disrupted in Burkitt’s Lymphomas. Cell. 1988;52:185–195. doi: 10.1016/0092-8674(88)90507-7. PubMed DOI

Marcu K.B., Bossone S.A., Patel A.J. Myc Function and Regulation. Annu. Rev. Biochem. 1992;61:809–860. doi: 10.1146/annurev.bi.61.070192.004113. PubMed DOI

Hann S.R., Dixit M., Sears R.C., Sealy L. The Alternatively Initiated C-Myc Proteins Differentially Regulate Transcription through a Noncanonical DNA-Binding Site. Genes Dev. 1994;8:2441–2452. doi: 10.1101/gad.8.20.2441. PubMed DOI

Cory S. Activation of Cellular Oncogenes in Hemopoietic Cells by Chromosome Translocation. Adv. Cancer Res. 1986;47:189–234. doi: 10.1016/s0065-230x(08)60200-6. PubMed DOI

Battey J., Moulding C., Taub R., Murphy W., Stewart T., Potter H., Lenoir G., Leder P. The Human C-Myc Oncogene: Structural Consequences of Translocation into the IgH Locus in Burkitt Lymphoma. Cell. 1983;34:779–787. doi: 10.1016/0092-8674(83)90534-2. PubMed DOI

Bernard O., Cory S., Gerondakis S., Webb E., Adams J.M. Sequence of the Murine and Human Cellular Myc Oncogenes and Two Modes of Myc Transcription Resulting from Chromosome Translocation in B Lymphoid Tumours. EMBO J. 1983;2:2375–2383. doi: 10.1002/j.1460-2075.1983.tb01749.x. PubMed DOI PMC

Bentley D.L., Groudine M. A Block to Elongation Is Largely Responsible for Decreased Transcription of C-Myc in Differentiated HL60 Cells. Nature. 1986;321:702–706. doi: 10.1038/321702a0. PubMed DOI

Nepveu A., Marcu K.B. Intragenic Pausing and Anti-Sense Transcription within the Murine c-Myc Locus. EMBO J. 1986;5:2859–2865. doi: 10.1002/j.1460-2075.1986.tb04580.x. PubMed DOI PMC

Yang J.Q., Remmers E.F., Marcu K.B. The First Exon of the C-Myc Proto-Oncogene Contains a Novel Positive Control Element. EMBO J. 1986;5:3553–3562. doi: 10.1002/j.1460-2075.1986.tb04682.x. PubMed DOI PMC

Nerlov C. The C/EBP Family of Transcription Factors: A Paradigm for Interaction between Gene Expression and Proliferation Control. Trends Cell Biol. 2007;17:318–324. doi: 10.1016/j.tcb.2007.07.004. PubMed DOI

Baluapuri A., Wolf E., Eilers M. Target Gene-Independent Functions of MYC Oncoproteins. Nat. Rev. Mol. Cell Biol. 2020;21:255–267. doi: 10.1038/s41580-020-0215-2. PubMed DOI PMC

Philipp A., Schneider A., Väsrik I., Finke K., Xiong Y., Beach D., Alitalo K., Eilers M. Repression of Cyclin D1: A Novel Function of MYC. Mol. Cell. Biol. 1994;14:4032–4043. doi: 10.1128/mcb.14.6.4032-4043.1994. PubMed DOI PMC

Freytag S.O., Geddes T.J. Reciprocal Regulation of Adipogenesis by Myc and C/EBP Alpha. Science. 1992;256:379–382. doi: 10.1126/science.256.5055.379. PubMed DOI

Hann S.R., Sloan-Brown K., Spotts G.D. Translational Activation of the Non-AUG-Initiated c-Myc 1 Protein at High Cell Densities Due to Methionine Deprivation. Genes Dev. 1992;6:1229–1240. doi: 10.1101/gad.6.7.1229. PubMed DOI

Blalock W.L., Piazzi M., Bavelloni A., Raffini M., Faenza I., D’Angelo A., Cocco L. Identification of the PKR Nuclear Interactome Reveals Roles in Ribosome Biogenesis, mRNA Processing and Cell Division. J. Cell Physiol. 2014;229:1047–1060. doi: 10.1002/jcp.24529. PubMed DOI

Umek R.M., Friedman A.D., McKnight S.L. CCAAT-Enhancer Binding Protein: A Component of a Differentiation Switch. Science. 1991;251:288–292. doi: 10.1126/science.1987644. PubMed DOI

Xiao Q., Claassen G., Shi J., Adachi S., Sedivy J., Hann S.R. Transactivation-Defective c-MycS Retains the Ability to Regulate Proliferation and Apoptosis. Genes Dev. 1998;12:3803–3808. doi: 10.1101/gad.12.24.3803. PubMed DOI PMC

Spotts G.D., Patel S.V., Xiao Q., Hann S.R. Identification of Downstream-Initiated c-Myc Proteins Which Are Dominant-Negative Inhibitors of Transactivation by Full-Length c-Myc Proteins. Mol. Cell. Biol. 1997;17:1459–1468. doi: 10.1128/MCB.17.3.1459. PubMed DOI PMC

Cazalla D., Zhu J., Manche L., Huber E., Krainer A.R., Cáceres J.F. Nuclear Export and Retention Signals in the RS Domain of SR Proteins. Mol. Cell. Biol. 2002;22:6871–6882. doi: 10.1128/MCB.22.19.6871-6882.2002. PubMed DOI PMC

Galmozzi E., Casalini P., Iorio M.V., Casati B., Olgiati C., Ménard S. HER2 Signaling Enhances 5′UTR-Mediated Translation of c-Myc mRNA. J. Cell Physiol. 2004;200:82–88. doi: 10.1002/jcp.20012. PubMed DOI

Notari M., Neviani P., Santhanam R., Blaser B.W., Chang J.-S., Galietta A., Willis A.E., Roy D.C., Caligiuri M.A., Marcucci G., et al. A MAPK/HNRPK Pathway Controls BCR/ABL Oncogenic Potential by Regulating MYC mRNA Translation. Blood. 2006;107:2507–2516. doi: 10.1182/blood-2005-09-3732. PubMed DOI PMC

Stoneley M., Paulin F.E., Le Quesne J.P., Chappell S.A., Willis A.E. C-Myc 5′ Untranslated Region Contains an Internal Ribosome Entry Segment. Oncogene. 1998;16:423–428. doi: 10.1038/sj.onc.1201763. PubMed DOI

Le Quesne J.P., Stoneley M., Fraser G.A., Willis A.E. Derivation of a Structural Model for the C-Myc IRES. J. Mol. Biol. 2001;310:111–126. doi: 10.1006/jmbi.2001.4745. PubMed DOI

Ji M.H., Kim S.-K., Kim C.-Y., Phi J.H., Jun H.J., Blume S.W., Choi H.S. Physiological Expression and Accumulation of the Products of Two Upstream Open Reading Frames Mrtl and MycHex1 Along With P64 and P67 Myc From the Human C-Myc Locus. J. Cell. Biochem. 2016;117:1407–1418. doi: 10.1002/jcb.25431. PubMed DOI

Thiry M., Lafontaine D.L.J. Birth of a Nucleolus: The Evolution of Nucleolar Compartments. Trends Cell Biol. 2005;15:194–199. doi: 10.1016/j.tcb.2005.02.007. PubMed DOI

Mao Y.S., Zhang B., Spector D.L. Biogenesis and Function of Nuclear Bodies. Trends Genet. 2011;27:295–306. doi: 10.1016/j.tig.2011.05.006. PubMed DOI PMC

Gazin C., Rigolet M., Briand J.P., Van Regenmortel M.H., Galibert F. Immunochemical Detection of Proteins Related to the Human C-Myc Exon 1. EMBO J. 1986;5:2241–2250. doi: 10.1002/j.1460-2075.1986.tb04491.x. PubMed DOI PMC

Fricker M., Hollinshead M., White N., Vaux D. Interphase Nuclei of Many Mammalian Cell Types Contain Deep, Dynamic, Tubular Membrane-Bound Invaginations of the Nuclear Envelope. J. Cell Biol. 1997;136:531–544. doi: 10.1083/jcb.136.3.531. PubMed DOI PMC

Broers J.L., Machiels B.M., van Eys G.J., Kuijpers H.J., Manders E.M., van Driel R., Ramaekers F.C. Dynamics of the Nuclear Lamina as Monitored by GFP-Tagged A-Type Lamins. Pt 20J. Cell Sci. 1999;112:3463–3475. doi: 10.1242/jcs.112.20.3463. PubMed DOI

Johnson N., Krebs M., Boudreau R., Giorgi G., LeGros M., Larabell C. Actin-Filled Nuclear Invaginations Indicate Degree of Cell de-Differentiation. Differentiation. 2003;71:414–424. doi: 10.1046/j.1432-0436.2003.7107003.x. PubMed DOI

Lagace T.A., Ridgway N.D. The Rate-Limiting Enzyme in Phosphatidylcholine Synthesis Regulates Proliferation of the Nucleoplasmic Reticulum. Mol. Biol. Cell. 2005;16:1120–1130. doi: 10.1091/mbc.e04-10-0874. PubMed DOI PMC

Echevarría W., Leite M.F., Guerra M.T., Zipfel W.R., Nathanson M.H. Regulation of Calcium Signals in the Nucleus by a Nucleoplasmic Reticulum. Nat. Cell Biol. 2003;5:440–446. doi: 10.1038/ncb980. PubMed DOI PMC

Mickleburgh I., Burtle B., Hollås H., Campbell G., Chrzanowska-Lightowlers Z., Vedeler A., Hesketh J. Annexin A2 Binds to the Localization Signal in the 3′ Untranslated Region of c-Myc mRNA. FEBS J. 2005;272:413–421. doi: 10.1111/j.1742-4658.2004.04481.x. PubMed DOI

Zaidi S.K., Young D.W., Javed A., Pratap J., Montecino M., van Wijnen A., Lian J.B., Stein J.L., Stein G.S. Nuclear Microenvironments in Biological Control and Cancer. Nat. Rev. Cancer. 2007;7:454–463. doi: 10.1038/nrc2149. PubMed DOI

Marinkovic T., Marinkovic D. Obscure Involvement of MYC in Neurodegenerative Diseases and Neuronal Repair. Mol. Neurobiol. 2021;58:4169–4177. doi: 10.1007/s12035-021-02406-w. PubMed DOI

Madden S.K., de Araujo A.D., Gerhardt M., Fairlie D.P., Mason J.M. Taking the Myc out of Cancer: Toward Therapeutic Strategies to Directly Inhibit c-Myc. Mol. Cancer. 2021;20:3. doi: 10.1186/s12943-020-01291-6. PubMed DOI PMC

Ahmadi S.E., Rahimi S., Zarandi B., Chegeni R., Safa M. MYC: A Multipurpose Oncogene with Prognostic and Therapeutic Implications in Blood Malignancies. J. Hematol. Oncol. 2021;14:121. doi: 10.1186/s13045-021-01111-4. PubMed DOI PMC

Whitfield J.R., Soucek L. The Long Journey to Bring a Myc Inhibitor to the Clinic. J. Cell Biol. 2021;220:202103090. doi: 10.1083/jcb.202103090. PubMed DOI PMC

Vaklavas C., Meng Z., Choi H., Grizzle W.E., Zinn K.R., Blume S.W. Small Molecule Inhibitors of IRES-Mediated Translation. Cancer Biol. Ther. 2015;16:1471–1485. doi: 10.1080/15384047.2015.1071729. PubMed DOI PMC

Vaklavas C., Grizzle W.E., Choi H., Meng Z., Zinn K.R., Shrestha K., Blume S.W. IRES Inhibition Induces Terminal Differentiation and Synchronized Death in Triple-Negative Breast Cancer and Glioblastoma Cells. Tumour Biol. 2016;37:13247–13264. doi: 10.1007/s13277-016-5161-4. PubMed DOI PMC

Shi Y., Sun F., Cheng Y., Holmes B., Dhakal B., Gera J.F., Janz S., Lichtenstein A. Critical Role for Cap-Independent c-MYC Translation in Progression of Multiple Myeloma. Mol. Cancer Ther. 2022;21:502–510. doi: 10.1158/1535-7163.MCT-21-0016. PubMed DOI PMC

Holmes B., Lee J., Landon K.A., Benavides-Serrato A., Bashir T., Jung M.E., Lichtenstein A., Gera J. Mechanistic Target of Rapamycin (mTOR) Inhibition Synergizes with Reduced Internal Ribosome Entry Site (IRES)-Mediated Translation of Cyclin D1 and c-MYC mRNAs to Treat Glioblastoma. J. Biol. Chem. 2016;291:14146–14159. doi: 10.1074/jbc.M116.726927. PubMed DOI PMC

Piazzi M., Bavelloni A., Faenza I., Blalock W. Glycogen Synthase Kinase (GSK)-3 and the Double-Strand RNA-Dependent Kinase, PKR: When Two Kinases for the Common Good Turn Bad. Biochim. Biophys. Acta Mol. Cell Res. 2020;1867:118769. doi: 10.1016/j.bbamcr.2020.118769. PubMed DOI PMC

Vaklavas C., Zinn K.R., Samuel S.L., Meng Z., Grizzle W.E., Choi H., Blume S.W. Translational Control of the Undifferentiated Phenotype in ER-positive Breast Tumor Cells: Cytoplasmic Localization of ERα and Impact of IRES Inhibition. Oncol. Rep. 2018;39:2482–2498. doi: 10.3892/or.2018.6332. PubMed DOI PMC

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