c-Myc

Summary

Gene Symbol: c-Myc
Description: MYC proto-oncogene, bHLH transcription factor
Alias: MRTL, MYCC, bHLHe39, c-Myc, myc proto-oncogene protein, avian myelocytomatosis viral oncogene homolog, class E basic helix-loop-helix protein 39, myc-related translation/localization regulatory factor, proto-oncogene c-Myc, transcription factor p64, v-myc avian myelocytomatosis viral oncogene homolog, v-myc myelocytomatosis viral oncogene homolog
Species: human
Products:     c-Myc

Top Publications

  1. Hu S, Xu Monette Z, Tzankov A, Green T, Wu L, Balasubramanyam A, et al. MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Pro. Blood. 2013;121:4021-31; quiz 4250 pubmed publisher
    ..In conclusion, the data suggest that MYC/BCL2 coexpression, rather than cell-of-origin classification, is a better predictor of prognosis in patients with DLBCL treated with R-CHOP. ..
  2. Porro A, Iraci N, Soverini S, Diolaiti D, Gherardi S, Terragna C, et al. c-MYC oncoprotein dictates transcriptional profiles of ATP-binding cassette transporter genes in chronic myelogenous leukemia CD34+ hematopoietic progenitor cells. Mol Cancer Res. 2011;9:1054-66 pubmed publisher
  3. Johnson N, Slack G, Savage K, Connors J, Ben Neriah S, Rogic S, et al. Concurrent expression of MYC and BCL2 in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30:3452-9 pubmed
    ..Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis. ..
  4. Cho Y, Tsherniak A, Tamayo P, Santagata S, Ligon A, Greulich H, et al. Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J Clin Oncol. 2011;29:1424-30 pubmed publisher
    ..Our results detail the complex genomic heterogeneity of medulloblastomas and identify a previously unrecognized molecular subgroup with poor clinical outcome for which more effective therapeutic strategies should be developed. ..
  5. Goode E, Chenevix Trench G, Song H, Ramus S, Notaridou M, Lawrenson K, et al. A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nat Genet. 2010;42:874-9 pubmed publisher
    ..Analysis of HOXD1, MYC, TIPARP and SKAP1 at these loci and of BNC2 at 9p22 supports a functional role for these genes in ovarian cancer development. ..
  6. Darcy K, Brady W, Blancato J, Dickson R, Hoskins W, McGuire W, et al. Prognostic relevance of c-MYC gene amplification and polysomy for chromosome 8 in suboptimally-resected, advanced stage epithelial ovarian cancers: a Gynecologic Oncology Group study. Gynecol Oncol. 2009;114:472-9 pubmed publisher
    ..c-MYC amplification and polysomy 8 have limited predictive or prognostic value in suboptimally-resected, advanced stage EOC treated with platinum-based combination chemotherapy. ..
  7. Prensner J, Chen W, Han S, Iyer M, Cao Q, Kothari V, et al. The long non-coding RNA PCAT-1 promotes prostate cancer cell proliferation through cMyc. Neoplasia. 2014;16:900-8 pubmed publisher
    ..This work establishes a basis for the oncogenic role of PCAT-1 in cancer cell proliferation and is the first study to implicate lncRNAs in the regulation of cMyc in prostate cancer. ..
  8. Welcker M, Orian A, Grim J, Grim J, Eisenman R, Clurman B. A nucleolar isoform of the Fbw7 ubiquitin ligase regulates c-Myc and cell size. Curr Biol. 2004;14:1852-7 pubmed
    ..We suggest that interactions between c-Myc and Fbw7gamma within the nucleolus regulate c-Myc's growth-promoting function and that c-Myc activation is likely to be an important oncogenic consequence of Fbw7 loss in cancers. ..
  9. Yu M, Schreek S, Cerni C, Schamberger C, Lesniewicz K, Poreba E, et al. PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation. Oncogene. 2005;24:1982-93 pubmed
    ..Together, our findings define a novel PARP enzyme involved in the control of cell proliferation. ..

More Information

Publications302 found, 100 shown here

  1. Guney I, Wu S, Sedivy J. Reduced c-Myc signaling triggers telomere-independent senescence by regulating Bmi-1 and p16(INK4a). Proc Natl Acad Sci U S A. 2006;103:3645-50 pubmed
    ..A mechanism for limiting the proliferation of damaged or otherwise physiologically compromised cells would be expected to have important consequences on the generation of replicatively senescent cells during organismal aging. ..
  2. Gurel B, Iwata T, Koh C, Jenkins R, Lan F, Van Dang C, et al. Nuclear MYC protein overexpression is an early alteration in human prostate carcinogenesis. Mod Pathol. 2008;21:1156-67 pubmed publisher
  3. Watanabe K, Ozaki T, Nakagawa T, Miyazaki K, Takahashi M, Hosoda M, et al. Physical interaction of p73 with c-Myc and MM1, a c-Myc-binding protein, and modulation of the p73 function. J Biol Chem. 2002;277:15113-23 pubmed
    ..Expression of MM1 strongly reduced the c-Myc-mediated inhibitory activity on p73 alpha. These results suggest that MM1 may act as a molecular partner for p73 to prevent the c-Myc-mediated inhibitory effect on its activity. ..
  4. David C, Chen M, Assanah M, Canoll P, Manley J. HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature. 2010;463:364-8 pubmed publisher
    ..Our results thus define a pathway that regulates an alternative splicing event required for tumour cell proliferation. ..
  5. Taira T, Sawai M, Ikeda M, Tamai K, Iguchi Ariga S, Ariga H. Cell cycle-dependent switch of up-and down-regulation of human hsp70 gene expression by interaction between c-Myc and CBF/NF-Y. J Biol Chem. 1999;274:24270-9 pubmed
    ..The results indicate that the cell cycle-dependent expression of the hsp70 gene is regulated by the intracellular amount of c-Myc through the complex formation states between CBF/NF-Y and c-Myc. ..
  6. Frank S, Schroeder M, Fernandez P, Taubert S, Amati B. Binding of c-Myc to chromatin mediates mitogen-induced acetylation of histone H4 and gene activation. Genes Dev. 2001;15:2069-82 pubmed
    ..Myc therefore governs a step, most likely H4 acetylation, that is required but not sufficient for transcriptional activation. We propose that Myc acts as a permissive factor, allowing additional signals to activate target promoters. ..
  7. Wang C, Mayer J, Mazumdar A, Fertuck K, Kim H, Brown M, et al. Estrogen induces c-myc gene expression via an upstream enhancer activated by the estrogen receptor and the AP-1 transcription factor. Mol Endocrinol. 2011;25:1527-38 pubmed publisher
    ..These results solve the long-standing question in the field of endocrinology of how estrogen induces c-myc expression. ..
  8. Roderick J, Tesell J, Shultz L, Brehm M, Greiner D, Harris M, et al. c-Myc inhibition prevents leukemia initiation in mice and impairs the growth of relapsed and induction failure pediatric T-ALL cells. Blood. 2014;123:1040-50 pubmed publisher
    ..These findings demonstrate a critical role for c-Myc in LIC maintenance and provide evidence that MYC inhibition may be an effective therapy for relapsed/IF T-ALL patients. ..
  9. Seo H, Kim J, Bae S, Soh J, Lee Y. Cdk5-mediated phosphorylation of c-Myc on Ser-62 is essential in transcriptional activation of cyclin B1 by cyclin G1. J Biol Chem. 2008;283:15601-10 pubmed publisher
    ..Taken together, the results of this study indicate that Cdk5 activation in cells that overexpress cyclin G1 leads to c-Myc phosphorylation on Ser-62, which is responsible for cyclin G1-mediated transcriptional activation of cyclin B1. ..
  10. Larramendy M, Niini T, Elonen E, Nagy B, Ollila J, Vihinen M, et al. Overexpression of translocation-associated fusion genes of FGFRI, MYC, NPMI, and DEK, but absence of the translocations in acute myeloid leukemia. A microarray analysis. Haematologica. 2002;87:569-77 pubmed
    ..Clinical and prognostic significance of differential gene expression should be studied with a larger series of patients by using other techniques, such as quantitative real-time PCR. ..
  11. Sachdeva M, Zhu S, Wu F, Wu H, Walia V, Kumar S, et al. p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci U S A. 2009;106:3207-12 pubmed publisher
  12. Leoni B, Natoli M, Nardella M, Bucci B, Zucco F, D Agnano I, et al. Differentiation of Caco-2 cells requires both transcriptional and post-translational down-regulation of Myc. Differentiation. 2012;83:116-27 pubmed publisher
    ..Moreover, we found a strong correlation between Myc protein downregulation and the expression of the transcription factor Cdx2, suggesting the existence of a regulative link between these two proteins. ..
  13. Chesi M, Robbiani D, Sebag M, Chng W, Affer M, Tiedemann R, et al. AID-dependent activation of a MYC transgene induces multiple myeloma in a conditional mouse model of post-germinal center malignancies. Cancer Cell. 2008;13:167-80 pubmed publisher
  14. Ruggero D, Montanaro L, Ma L, Xu W, Londei P, Cordon Cardo C, et al. The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis. Nat Med. 2004;10:484-6 pubmed
    ..Our results implicate activation of eIF-4E as a key event in oncogenic transformation by phosphoinositide-3 kinase and Akt. ..
  15. Zhang W, Kater A, Widhopf G, Chuang H, Enzler T, James D, et al. B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2010;107:18956-60 pubmed publisher
  16. Poortinga G, Hannan K, Snelling H, Walkley C, Jenkins A, Sharkey K, et al. MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation. EMBO J. 2004;23:3325-35 pubmed
  17. Staller P, Peukert K, Kiermaier A, Seoane J, Lukas J, Karsunky H, et al. Repression of p15INK4b expression by Myc through association with Miz-1. Nat Cell Biol. 2001;3:392-9 pubmed
    ..Alleles of c-myc that are unable to bind to Miz-1 fail to inhibit accumulation of p15INK4b messenger RNA in primary cells and are, as a consequence, deficient in immortalization. ..
  18. Oster S, Mao D, Kennedy J, Penn L. Functional analysis of the N-terminal domain of the Myc oncoprotein. Oncogene. 2003;22:1998-2010 pubmed
    ..Indeed, a close association of Myc repression and apoptosis was also observed. ..
  19. Chan J, Hannan K, Riddell K, Ng P, Peck A, Lee R, et al. AKT promotes rRNA synthesis and cooperates with c-MYC to stimulate ribosome biogenesis in cancer. Sci Signal. 2011;4:ra56 pubmed publisher
    ..These data indicate that decreased ribosome biogenesis is likely to be a fundamental component of the therapeutic response to AKT inhibitors in cancer. ..
  20. Fang Z, Dong C, Chen Z, Zhou B, Liu N, Lan H, et al. Transcriptional regulation of survivin by c-Myc in BCR/ABL-transformed cells: implications in anti-leukaemic strategy. J Cell Mol Med. 2009;13:2039-52 pubmed publisher
    ..These results suggest that the interference with this circuitry might be a potential utility for CML treatment. ..
  21. Dueck A, Reinholz M, Geiger X, Tenner K, Ballman K, Jenkins R, et al. Impact of c-MYC protein expression on outcome of patients with early-stage HER2+ breast cancer treated with adjuvant trastuzumab NCCTG (alliance) N9831. Clin Cancer Res. 2013;19:5798-807 pubmed publisher
    ..56 (P = 0.02) and 0.89 (P = 0.49), respectively (P(interaction) = 0.17). Our data do not support an impact of tumor MYC protein expression on differential benefit from adjuvant trastuzumab. ..
  22. Cowling V, Chandriani S, Whitfield M, Cole M. A conserved Myc protein domain, MBIV, regulates DNA binding, apoptosis, transformation, and G2 arrest. Mol Cell Biol. 2006;26:4226-39 pubmed
    ..Thus, this conserved domain has an unexpected role in Myc DNA binding activity. These data also provide a novel separation of Myc functions linked to the modulation of DNA binding activity. ..
  23. Shi Y, Frost P, Hoang B, Benavides A, Gera J, Lichtenstein A. IL-6-induced enhancement of c-Myc translation in multiple myeloma cells: critical role of cytoplasmic localization of the rna-binding protein hnRNP A1. J Biol Chem. 2011;286:67-78 pubmed publisher
    ..Thus, IL-6 activates c-Myc translation in MM cells by inducing A1 phosphorylation and cytoplasmic localization in a p38-dependent fashion. These data suggest A1 as a potential therapeutic target in MM. ..
  24. Zhang H, Chen Z, Li S, Bai W, Cheng N, Wang J. Clinical significance and prognosis of MYC translocation in diffuse large B-cell lymphoma. Hematol Oncol. 2011;29:185-9 pubmed publisher
    ..This may be a clinical characteristic that is specific to Chinese patients. Because only a few patients received rituximab, its usefulness could not be assessed. Future studies with larger numbers of patients are required. ..
  25. Tsiatis A, Herceg M, Keedy V, Halpern J, Holt G, Schwartz H, et al. Prognostic significance of c-Myc expression in soft tissue leiomyosarcoma. Mod Pathol. 2009;22:1432-8 pubmed publisher
    ..The expression of this oncoprotein may represent a useful prognostic marker and potential therapeutic target in leiomyosarcoma. ..
  26. Fujioka Y, Taira T, Maeda Y, Tanaka S, Nishihara H, Iguchi Ariga S, et al. MM-1, a c-Myc-binding protein, is a candidate for a tumor suppressor in leukemia/lymphoma and tongue cancer. J Biol Chem. 2001;276:45137-44 pubmed
    ..The results suggest that MM-1 is a novel candidate for a tumor suppressor that controls the transcriptional activity of c-Myc. ..
  27. Gomez Roman N, Grandori C, Eisenman R, White R. Direct activation of RNA polymerase III transcription by c-Myc. Nature. 2003;421:290-4 pubmed
    ..These results suggest that activation of pol III may have a role in the ability of c-Myc to stimulate cell growth. ..
  28. Von Bueren A, Shalaby T, Oehler Janne C, Arnold L, Stearns D, Eberhart C, et al. RNA interference-mediated c-MYC inhibition prevents cell growth and decreases sensitivity to radio- and chemotherapy in childhood medulloblastoma cells. BMC Cancer. 2009;9:10 pubmed publisher
    ..Therefore, targeting c-MYC might be of therapeutic benefit when used sequentially with chemo- and radiotherapy rather than concomitantly. ..
  29. McEwan I, Dahlman Wright K, Ford J, Wright A. Functional interaction of the c-Myc transactivation domain with the TATA binding protein: evidence for an induced fit model of transactivation domain folding. Biochemistry. 1996;35:9584-93 pubmed
    ..These data support a model in which target factors induce or stabilize a structural conformation in activator proteins during transcriptional transactivation. ..
  30. McMahon S, Wood M, Cole M. The essential cofactor TRRAP recruits the histone acetyltransferase hGCN5 to c-Myc. Mol Cell Biol. 2000;20:556-62 pubmed
  31. Yochum G, Cleland R, Goodman R. A genome-wide screen for beta-catenin binding sites identifies a downstream enhancer element that controls c-Myc gene expression. Mol Cell Biol. 2008;28:7368-79 pubmed publisher
    ..Our findings indicate that a downstream enhancer element provides the principal regulation of c-Myc expression. ..
  32. Adhikary S, Marinoni F, Hock A, Hulleman E, Popov N, Beier R, et al. The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation. Cell. 2005;123:409-21 pubmed
    ..Our results suggest that site-specific ubiquitination regulates the switch between an activating and a repressive state of the Myc protein, and they suggest a strategy to interfere with Myc function in vivo. ..
  33. Xiao W, Wang J, Ou C, Zhang Y, Ma L, Weng W, et al. Mutual interaction between YAP and c-Myc is critical for carcinogenesis in liver cancer. Biochem Biophys Res Commun. 2013;439:167-72 pubmed publisher
  34. Mannava S, Grachtchouk V, Wheeler L, Im M, Zhuang D, Slavina E, et al. Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells. Cell Cycle. 2008;7:2392-400 pubmed
    ..Our data establish a novel functional link between C-MYC and dNTP metabolism and identify its role in proliferation of tumor cells. ..
  35. Gomez Casares M, García Alegría E, López Jorge C, Ferrandiz N, Blanco R, Alvarez S, et al. MYC antagonizes the differentiation induced by imatinib in chronic myeloid leukemia cells through downregulation of p27(KIP1.). Oncogene. 2013;32:2239-46 pubmed publisher
    ..The results suggest that, although MYC deregulation does not directly confer resistance to imatinib, it might be a factor that contributes to progression of CML through the inhibition of differentiation. ..
  36. Ott G, Rosenwald A, Campo E. Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification. Blood. 2013;122:3884-91 pubmed publisher
    ..In this review, we integrate all of this new information and discuss perspectives, challenges, and open questions for the diagnosis and management of patients with MYC-driven aggressive B-cell lymphomas. ..
  37. Horiuchi D, Kusdra L, Huskey N, Chandriani S, Lenburg M, Gonzalez Angulo A, et al. MYC pathway activation in triple-negative breast cancer is synthetic lethal with CDK inhibition. J Exp Med. 2012;209:679-96 pubmed publisher
    ..These results indicate that aggressive breast tumors with elevated MYC are uniquely sensitive to CDK inhibitors. ..
  38. de Nigris F, Botti C, Rossiello R, Crimi E, Sica V, Napoli C. Cooperation between Myc and YY1 provides novel silencing transcriptional targets of alpha3beta1-integrin in tumour cells. Oncogene. 2007;26:382-94 pubmed
    ..YY1 regulated negatively the Myc activity through a direct interaction with the Myc/Max and deacetylase complexes. This represents a novel silencing mechanism with broad implications in the transcription machinery of tumours. ..
  39. Lal A, Navarro F, Maher C, Maliszewski L, Yan N, O Day E, et al. miR-24 Inhibits cell proliferation by targeting E2F2, MYC, and other cell-cycle genes via binding to "seedless" 3'UTR microRNA recognition elements. Mol Cell. 2009;35:610-25 pubmed publisher
    ..The E2F2 3'UTR lacks a predicted miR-24 recognition element. In fact, miR-24 regulates expression of E2F2, MYC, AURKB, CCNA2, CDC2, CDK4, and FEN1 by recognizing seedless but highly complementary sequences. ..
  40. Patel J, McMahon S. BCL2 is a downstream effector of MIZ-1 essential for blocking c-MYC-induced apoptosis. J Biol Chem. 2007;282:5-13 pubmed
    ..These data define a genetic pathway that helps to explain historical observations documenting cooperation between c-MYC and BCL2 overexpression in human cancer. ..
  41. Perez Sayans M, Suárez Peñaranda J, Pilar G, Barros Angueira F, Gandara Rey J, Garcia Garcia A. What real influence does the proto-oncogene c-myc have in OSCC behavior?. Oral Oncol. 2011;47:688-92 pubmed publisher
  42. Mori K, Maeda Y, Kitaura H, Taira T, Iguchi Ariga S, Ariga H. MM-1, a novel c-Myc-associating protein that represses transcriptional activity of c-Myc. J Biol Chem. 1998;273:29794-800 pubmed
    ..Furthermore, MM-1 repressed the activation of E-box-dependent transcription by c-Myc. ..
  43. Feng X, Liang Y, Liang M, Zhai W, Lin X. Direct interaction of c-Myc with Smad2 and Smad3 to inhibit TGF-beta-mediated induction of the CDK inhibitor p15(Ink4B). Mol Cell. 2002;9:133-43 pubmed
    ..These results suggest that oncogenic c-Myc promotes cell growth and cancer development partly by inhibiting the growth inhibitory functions of Smads. ..
  44. Yeager M, Orr N, Hayes R, Jacobs K, Kraft P, Wacholder S, et al. Genome-wide association study of prostate cancer identifies a second risk locus at 8q24. Nat Genet. 2007;39:645-9 pubmed
    ..We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%). ..
  45. Wei W, Jin J, Schlisio S, Harper J, Kaelin W. The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase. Cancer Cell. 2005;8:25-33 pubmed
    ..These findings explain the enhanced stability and oncogenicity of v-Jun relative to its cellular counterpart and reveal that GSK3 and Fbw7 coordinately regulate c-Jun and c-Myc. ..
  46. Mao B, Zhao G, Lv X, Chen H, Xue Z, Yang B, et al. Sirt1 deacetylates c-Myc and promotes c-Myc/Max association. Int J Biochem Cell Biol. 2011;43:1573-81 pubmed publisher
    ..Thus, our results demonstrate the positive effect of Sirt1 on c-Myc activity by efficiently enhancing c-Myc/Max association in human leukemia cell line K562, suggesting a potential role of Sirt1 in tumorigenesis. ..
  47. Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V, et al. The p400 complex is an essential E1A transformation target. Cell. 2001;106:297-307 pubmed
    ..Furthermore, E1A and c-myc each alter the subunit composition of p400 complexes, implying that physiological p400 complex formation contributes to transformation suppression. ..
  48. Williams K, Fernandez S, Stien X, Ishii K, Love H, Lau Y, et al. Unopposed c-MYC expression in benign prostatic epithelium causes a cancer phenotype. Prostate. 2005;63:369-84 pubmed
    ..By using a retroviral infection strategy followed by tissue recombination we have created a model of human prostate cancer that demonstrates that the c-MYC gene is sufficient to induce carcinogenesis. ..
  49. Stasik C, Nitta H, Zhang W, Mosher C, Cook J, Tubbs R, et al. Increased MYC gene copy number correlates with increased mRNA levels in diffuse large B-cell lymphoma. Haematologica. 2010;95:597-603 pubmed publisher
    ..MYC copy number changes are an additional possible molecular mechanism that may result in increased mRNA and, likely, high proliferation and poor outcome. ..
  50. Green T, Nielsen O, de Stricker K, Xu Monette Z, Young K, Møller M. High levels of nuclear MYC protein predict the presence of MYC rearrangement in diffuse large B-cell lymphoma. Am J Surg Pathol. 2012;36:612-9 pubmed publisher
    ..Area under the receiver operating characteristic curve was 0.992, indicating that immunostaining for Myc protein is an excellent screening test to predict whether an MYC rearrangement is present. ..
  51. Wirtenberger M, Hemminki K, Forsti A, Klaes R, Schmutzler R, Grzybowska E, et al. c-MYC Asn11Ser is associated with increased risk for familial breast cancer. Int J Cancer. 2005;117:638-42 pubmed
    ..Due to the pivotal role of c-MYC in diverse tumours, this variant might affect the genetic susceptibility of other cancers as well. ..
  52. Hemann M, Bric A, Teruya Feldstein J, Herbst A, Nilsson J, Cordon Cardo C, et al. Evasion of the p53 tumour surveillance network by tumour-derived MYC mutants. Nature. 2005;436:807-11 pubmed
  53. Bretones G, Acosta J, Caraballo J, Ferrandiz N, Gomez Casares M, Albajar M, et al. SKP2 oncogene is a direct MYC target gene and MYC down-regulates p27(KIP1) through SKP2 in human leukemia cells. J Biol Chem. 2011;286:9815-25 pubmed publisher
    ..Our data show that SKP2 is a direct MYC target gene and that MYC-mediated SKP2 induction leads to reduced p27 levels. The results suggest the induction of SKP2 oncogene as a new mechanism for MYC-dependent transformation. ..
  54. KINNEY E, Tanida S, Rodrigue A, Johnson J, Tompkins V, Sakamuro D. Adenovirus E1A oncoprotein liberates c-Myc activity to promote cell proliferation through abating Bin1 expression via an Rb/E2F1-dependent mechanism. J Cell Physiol. 2008;216:621-31 pubmed publisher
    ..We propose a novel G1 arrest signaling mechanism by which Rb indirectly curbs oncogenic c-Myc activity via sustaining Bin1 expression. ..
  55. Calcagno D, Leal M, Assumpcao P, Smith M, Burbano R. MYC and gastric adenocarcinoma carcinogenesis. World J Gastroenterol. 2008;14:5962-8 pubmed
    ..In the present review, we focus on the deregulation of the MYC oncogene in gastric adenocarcinoma carcinogenesis, including its association with Helicobacter pylori (H pylori) and clinical applications. ..
  56. von der Lehr N, Johansson S, Wu S, Bahram F, Castell A, Cetinkaya C, et al. The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription. Mol Cell. 2003;11:1189-200 pubmed
    ..The results suggest that Skp2 is a transcriptional cofactor for c-Myc and indicates a close relationship between transcription activation and transcription factor ubiquitination. ..
  57. Gombert W, Farris S, Rubio E, Morey Rosler K, Schubach W, Krumm A. The c-myc insulator element and matrix attachment regions define the c-myc chromosomal domain. Mol Cell Biol. 2003;23:9338-48 pubmed
    ..The MARs of the c-myc domain do not act to prevent the association of flanking regions with lysine 9-methylated histones, suggesting that they do not function as barrier elements. ..
  58. Felsher D, Zetterberg A, Zhu J, Tlsty T, Bishop J. Overexpression of MYC causes p53-dependent G2 arrest of normal fibroblasts. Proc Natl Acad Sci U S A. 2000;97:10544-8 pubmed
    ..The loss of p53 function seems to be one mechanism by which this relaxation commonly occurs. These findings dramatize how multiple genetic events can collaborate to produce neoplastic cells. ..
  59. Luscher B. Function and regulation of the transcription factors of the Myc/Max/Mad network. Gene. 2001;277:1-14 pubmed
    ..Thus the antagonism of Myc and Mad proteins is explained at the molecular level by the recruitment of opposing chromatin remodeling activities. ..
  60. Rodrik V, Zheng Y, Harrow F, Chen Y, Foster D. Survival signals generated by estrogen and phospholipase D in MCF-7 breast cancer cells are dependent on Myc. Mol Cell Biol. 2005;25:7917-25 pubmed
    ..The data also suggest that elevated PLD expression, which is common in breast cancer, confers E2 independence. ..
  61. Eberhart C, Kratz J, Wang Y, Summers K, Stearns D, Cohen K, et al. Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia. J Neuropathol Exp Neurol. 2004;63:441-9 pubmed
    ..The association we describe between c-myc expression, tumor anaplasia, and worse clinical outcomes provides further evidence for the importance of this oncogene in medulloblastoma pathobiology...
  62. Grandori C, Gomez Roman N, Felton Edkins Z, Ngouenet C, Galloway D, Eisenman R, et al. c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I. Nat Cell Biol. 2005;7:311-8 pubmed
    ..We propose that stimulation of rRNA synthesis by c-Myc is a key pathway driving cell growth and tumorigenesis. ..
  63. Park K, Krishnan V, O Malley B, Yamamoto Y, Gaynor R. Formation of an IKKalpha-dependent transcription complex is required for estrogen receptor-mediated gene activation. Mol Cell. 2005;18:71-82 pubmed
    ..These results suggest that IKKalpha plays a major role in regulating the biological effects of estrogen via its promoter association and modification of components of the transcription complex. ..
  64. Jones L, Wei G, Sevcikova S, Phan V, Jain S, Shieh A, et al. Gain of MYC underlies recurrent trisomy of the MYC chromosome in acute promyelocytic leukemia. J Exp Med. 2010;207:2581-94 pubmed publisher
    ..In addition, we found that human myeloid leukemias with trisomy 8 have increased MYC. These data show that gain of MYC can contribute to the pathogenic effect of the most common trisomy of human AML. ..
  65. Manner J, Radlwimmer B, Hohenberger P, Mössinger K, Küffer S, Sauer C, et al. MYC high level gene amplification is a distinctive feature of angiosarcomas after irradiation or chronic lymphedema. Am J Pathol. 2010;176:34-9 pubmed publisher
    ..This finding may have implications both for the diagnosis and treatment of these tumors. ..
  66. Koh C, Iwata T, Zheng Q, Bethel C, Yegnasubramanian S, De Marzo A. Myc enforces overexpression of EZH2 in early prostatic neoplasia via transcriptional and post-transcriptional mechanisms. Oncotarget. 2011;2:669-83 pubmed
    ..Further, the results implicate EZH2-driven mechanisms by which Myc may stimulate prostate tumor initiation and disease progression. ..
  67. Teng S, Chen Y, Su Y, Chou P, Chiang Y, Tseng S, et al. Direct activation of HSP90A transcription by c-Myc contributes to c-Myc-induced transformation. J Biol Chem. 2004;279:14649-55 pubmed
    ..These results indicate that by induction of HSP90A c-Myc may control the activity of multiple signal pathways involved in cellular transformation. ..
  68. Civenni G, Malek A, Albino D, García Escudero R, Napoli S, Di Marco S, et al. RNAi-mediated silencing of Myc transcription inhibits stem-like cell maintenance and tumorigenicity in prostate cancer. Cancer Res. 2013;73:6816-27 pubmed publisher
    ..More generally, our findings demonstrate the efficacy of RNAi-based transcriptional strategies and the potential to target regulatory noncoding paRNAs for therapeutic applications. ..
  69. Faiola F, Liu X, Lo S, Pan S, Zhang K, Lymar E, et al. Dual regulation of c-Myc by p300 via acetylation-dependent control of Myc protein turnover and coactivation of Myc-induced transcription. Mol Cell Biol. 2005;25:10220-34 pubmed
    ..Our results suggest dual roles for p300/CBP in Myc regulation: as a Myc coactivator that stabilizes Myc and as an inducer of Myc instability via direct Myc acetylation. ..
  70. Zippo A, De Robertis A, Serafini R, Oliviero S. PIM1-dependent phosphorylation of histone H3 at serine 10 is required for MYC-dependent transcriptional activation and oncogenic transformation. Nat Cell Biol. 2007;9:932-44 pubmed
  71. Salghetti S, Kim S, Tansey W. Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize Myc. EMBO J. 1999;18:717-26 pubmed
    ..Our data reveal a complex network of interactions regulating Myc destruction, and imply that enhanced protein stability contributes to oncogenic transformation by mutant Myc proteins. ..
  72. Mertz J, Conery A, Bryant B, Sandy P, Balasubramanian S, Mele D, et al. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A. 2011;108:16669-74 pubmed publisher
    ..These findings demonstrate that pharmacologic inhibition of MYC is achievable through targeting BET bromodomains. Such inhibitors may have clinical utility given the widespread pathogenetic role of MYC in cancer. ..
  73. Ma M, Li C, Zhang Y, Weng M, Zhang M, Qin Y, et al. Long non-coding RNA HOTAIR, a c-Myc activated driver of malignancy, negatively regulates miRNA-130a in gallbladder cancer. Mol Cancer. 2014;13:156 pubmed publisher
    ..Together, these results suggest that HOTAIR is a c-Myc-activated driver of malignancy, which acts in part through repression of miRNA-130a. ..
  74. Mallette F, Gaumont Leclerc M, Huot G, Ferbeyre G. Myc down-regulation as a mechanism to activate the Rb pathway in STAT5A-induced senescence. J Biol Chem. 2007;282:34938-44 pubmed
    ..These results uncover a novel mechanism to engage the Rb pathway in oncogene-induced senescence and indicate the existence of oncogene-specific pathways that regulate senescence. ..
  75. Yochum G, Sherrick C, MacPartlin M, Goodman R. A beta-catenin/TCF-coordinated chromatin loop at MYC integrates 5' and 3' Wnt responsive enhancers. Proc Natl Acad Sci U S A. 2010;107:145-50 pubmed publisher
    ..Thus, we propose that a distinct chromatin architecture coordinated by beta-catenin/TCF-bound WREs accompanies transcriptional activation of MYC gene expression. ..
  76. Wolfer A, Wittner B, Irimia D, Flavin R, Lupien M, Gunawardane R, et al. MYC regulation of a "poor-prognosis" metastatic cancer cell state. Proc Natl Acad Sci U S A. 2010;107:3698-703 pubmed publisher
    ..These results suggest that MYC oncogene activity (as marked by "poor-prognosis" signature expression) may be necessary for the translocation of poor-outcome human breast tumors to distant sites. ..
  77. Sjostrom S, Finn G, Hahn W, Rowitch D, Kenney A. The Cdk1 complex plays a prime role in regulating N-myc phosphorylation and turnover in neural precursors. Dev Cell. 2005;9:327-38 pubmed
    ..These findings provide a mechanism for promoting growth arrest in the final cycle of neural precursor proliferation competency, or for resetting the cell cycle in the G1 phase, by destabilizing N-myc in mitosis. ..
  78. Valentino C, Kendrick S, Johnson N, Gascoyne R, Chan W, Weisenburger D, et al. Colorimetric in situ hybridization identifies MYC gene signal clusters correlating with increased copy number, mRNA, and protein in diffuse large B-cell lymphoma. Am J Clin Pathol. 2013;139:242-54 pubmed publisher
    ..Clusters of MYC signals may be an underappreciated, but clinically important, feature of aggressive B-cell lymphomas with potential prognostic and therapeutic relevance. ..
  79. Yada M, Hatakeyama S, Kamura T, Nishiyama M, Tsunematsu R, Imaki H, et al. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J. 2004;23:2116-25 pubmed
    ..Accumulation of c-Myc was also apparent in mouse Fbw7-/- embryonic stem cells. These observations suggest that two F-box proteins, Fbw7 and Skp2, differentially regulate c-Myc stability by targeting MB1 and MB2, respectively. ..
  80. Zhuang D, Mannava S, Grachtchouk V, Tang W, Patil S, Wawrzyniak J, et al. C-MYC overexpression is required for continuous suppression of oncogene-induced senescence in melanoma cells. Oncogene. 2008;27:6623-34 pubmed publisher
    ..Our data suggest that one of the major functions of C-MYC overexpression in melanoma progression is to continuous suppress BRAF(V600E)- or NRAS(Q61R)-dependent senescence programs. ..
  81. Mott J, Kurita S, Cazanave S, Bronk S, Werneburg N, Fernandez Zapico M. Transcriptional suppression of mir-29b-1/mir-29a promoter by c-Myc, hedgehog, and NF-kappaB. J Cell Biochem. 2010;110:1155-64 pubmed publisher
    ..Thus, in addition to c-Myc, mir-29 expression can be suppressed by hedgehog signaling and inflammatory pathways, both commonly activated in the genesis of human malignancies. ..
  82. Park A, Lee S, Phi J, Wang K, Kim D, Cho B, et al. Prognostic classification of pediatric medulloblastoma based on chromosome 17p loss, expression of MYCC and MYCN, and Wnt pathway activation. Neuro Oncol. 2012;14:203-14 pubmed publisher
    ..prognostic determinants: loss of tumor suppressors (chromosome 17p) and high expression of oncogenes c-myc (MYCC) or N-myc (MYCN)...
  83. Karlsson A, Deb Basu D, Cherry A, Turner S, Ford J, Felsher D. Defective double-strand DNA break repair and chromosomal translocations by MYC overexpression. Proc Natl Acad Sci U S A. 2003;100:9974-9 pubmed
    ..Hence, MYC overexpression may be a previously undescribed example of a dominant mutator that may fuel tumorigenesis by inducing chromosomal damage. ..
  84. Cappellen D, Schlange T, Bauer M, Maurer F, Hynes N. Novel c-MYC target genes mediate differential effects on cell proliferation and migration. EMBO Rep. 2007;8:70-6 pubmed
    ..Our combined genomic and phenotypic analysis indicates that c-MYC functions are cellular-context-dependent and that selectively regulated genes are responsible for its differential properties. ..
  85. Gordan J, Lal P, Dondeti V, Letrero R, Parekh K, Oquendo C, et al. HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma. Cancer Cell. 2008;14:435-46 pubmed publisher
    ..These reproducible distinctions in ccRCC behavior delineate HIF-alpha effects on c-Myc in vivo and suggest molecular criteria for selecting targeted therapies. ..
  86. Wanzel M, Russ A, Kleine Kohlbrecher D, Colombo E, Pelicci P, Eilers M. A ribosomal protein L23-nucleophosmin circuit coordinates Mizl function with cell growth. Nat Cell Biol. 2008;10:1051-61 pubmed
    ..As L23 is encoded by a direct target gene of Myc, this regulatory circuit may provide a feedback mechanism that links translation of Myc target genes and cell growth to Miz1-dependent cell-cycle arrest. ..
  87. Junttila M, Puustinen P, Niemelä M, Ahola R, Arnold H, Böttzauw T, et al. CIP2A inhibits PP2A in human malignancies. Cell. 2007;130:51-62 pubmed
    ..Thus, our data show that CIP2A is a human oncoprotein that inhibits PP2A and stabilizes c-Myc in human malignancies. ..
  88. Gabrea A, Martelli M, Qi Y, Roschke A, Barlogie B, Shaughnessy J, et al. Secondary genomic rearrangements involving immunoglobulin or MYC loci show similar prevalences in hyperdiploid and nonhyperdiploid myeloma tumors. Genes Chromosomes Cancer. 2008;47:573-90 pubmed publisher
    ..We conclude that IG light chain and MYC rearrangements, as well as secondary IGH rearrangements, make similar contributions to the progression of both HRD and NHRD MM tumors. ..
  89. Khanna A, Böckelman C, Hemmes A, Junttila M, Wiksten J, Lundin M, et al. MYC-dependent regulation and prognostic role of CIP2A in gastric cancer. J Natl Cancer Inst. 2009;101:793-805 pubmed publisher
    ..CIP2A and MYC appear to be regulated in a positive feedback loop, wherein they promote each other's expression and gastric cancer cell proliferation. ..
  90. Ren J, Jin F, Yu Z, Zhao L, Wang L, Bai X, et al. MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency. Tumour Biol. 2013;34:3945-58 pubmed publisher
    ..The targeting of BRCA1 deficiency in combination with MYC-pathways inhibitors may provide a promising strategy for sporadic breast cancer care, the triple-negative subtype in particular. ..
  91. Walz S, Lorenzin F, Morton J, Wiese K, von Eyss B, Herold S, et al. Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles. Nature. 2014;511:483-7 pubmed publisher
    ..Third, complex formation with MIZ1 (also known as ZBTB17) mediates repression of multiple target genes by MYC and the ratio of MYC and MIZ1 bound to each promoter correlates with the direction of response...
  92. Costa Raiol L, Figueira Silva E, Mendes da Fonseca D, Leal M, Guimarães A, Calcagno D, et al. Interrelationship between MYC gene numerical aberrations and protein expression in individuals from northern Brazil with early gastric adenocarcinoma. Cancer Genet Cytogenet. 2008;181:31-5 pubmed publisher
    ..These novel findings concerning MYC copy number alteration in early gastric cancer suggest that MYC alteration is observed in the beginning of gastric carcinogenesis and could be used as a therapeutic target. ..