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Gene Review

Myc  -  myelocytomatosis oncogene

Mus musculus

Synonyms: AU016757, Myc proto-oncogene protein, Myc2, Niard, Nird, ...
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Disease relevance of Myc

  • Yet Kras-transformed mouse colonocytes lacking p53 formed indolent, poorly vascularized tumors, whereas additional transduction with a Myc-encoding retrovirus promoted vigorous vascularization and growth [1].
  • However, Myc is also induced in many postmitotic tissues, including adult myocardium, in response to stress where the predominant form of growth is an increase in cell size (hypertrophy) and not number [2].
  • We also found that cyclins E1 and E2 are expressed at high levels in mouse breast tumors driven by the Myc oncogene [3].
  • Transgenic progeny from one of these lines can be induced to develop T-ALL by injecting Cre RNA into one-cell-stage embryos, demonstrating the utility of the Cre/lox system in the zebrafish and providing an essential step in preparing this model for chemical and genetic screens designed to identify modifiers of Myc-induced T-ALL [4].
  • Remarkably, inactivation of even a single allele of Bim accelerated Myc-induced development of tumors, particularly acute B cell leukemia [5].
  • Our study demonstrates that 3' IgH enhancers alone can deregulate c-myc and initiate the development of BL-like lymphomas [6].
  • We show in a beta-cell tumor model that activation of Myc in vivo triggers rapid recruitment of mast cells to the tumor site-a recruitment that is absolutely required for macroscopic tumor expansion [7].

Psychiatry related information on Myc

  • Although approximately one-half of single transgenic c-myc virgin females also eventually developed mammary gland tumors, these were stochastic and arose after a long latency period of 9-12 months [8].
  • The effects of c-myc were further dissected by showing that c-myc can inhibit differentiation independently of Id, a negative regulator of muscle differentiation [9].

High impact information on Myc


Chemical compound and disease context of Myc


Biological context of Myc

  • Numerous experiments have also demonstrated a critical role for both Myc and Ras activities in allowing cell-cycle progression [18].
  • Our data suggest that Src kinases control the transcriptional activation of Myc [19].
  • This antagonism relates partly to their ability to compete with Myc for the protein Max and for consensus DNA binding sites and to recruit transcriptional co-repressors [20].
  • Our results show that Mxi1 is involved in the homeostasis of differentiated organ systems, acts as a tumour suppressor in vivo, and engages the Myc network in a functionally relevant manner [20].
  • Here we report that p53 and ARF also potentiate Myc-induced apoptosis in primary pre-B-cell cultures, and that spontaneous inactivation of the ARF-Mdm2-p53 pathway occurs frequently in tumors arising in Emu-myc transgenic mice [21].

Anatomical context of Myc


Associations of Myc with chemical compounds


Physical interactions of Myc


Enzymatic interactions of Myc

  • In the parental S194 cells, one allele of the c-myc was rearranged and its 5'-flanking region was partially deleted by recombination with the immunoglobulin C alpha gene [32].

Co-localisations of Myc


Regulatory relationships of Myc

  • The protracted latent period before the onset of frank disease likely reflects the ability of c-Myc to induce a p53-dependent apoptotic program that initially protects animals against tumor formation but is disabled when overtly malignant cells emerge [21].
  • Our results also establish a requirement for activated cyclin-dependent kinases (cdks), as v-Abl-dependent induction of c-myc transcription is blocked by cdk inhibitor p21 and induction of c-myc is accompanied by activation of cdk2 and cdk4 [27].
  • Ectopic c-Myc expression overrode apoptosis induced by TGF beta 1 [34].
  • Since we have demonstrated NF-kappa/Rel factors play a key role in transcriptional control of c-myc, we explored the effects of TGF beta1 on WEHI 231 immature B cells [34].
  • B cell growth is controlled by phosphatidylinosotol 3-kinase-dependent induction of Rel/NF-kappaB regulated c-myc transcription [35].
  • C-Myc-activated Casp3(-/-) mice were protected from streptozotocin-induced diabetes [36].

Other interactions of Myc

  • We suggest that interaction of Myn with c-Myc stabilizes sequence-specific DNA binding in vivo [28].
  • In the hematopoietic cell line BAF-B03, the expression of any two of lckF505 (an active form of p56lck), Bcl-2, or c-Myc is sufficient to promote transit of the cell cycle, regardless of the activation state of the third pathway [37].
  • In contrast, Fos and Jun, but not Myc, rescued the block induced by dominant negative Ras [19].
  • Ha-ras and c-myc oncogene expression interferes with morphological and functional differentiation of mammary epithelial cells in single and double transgenic mice [38].
  • However, in contrast to other aspects of v-Abl signaling, induction of c-myc transcription is independent of the Rac GTPase [27].

Analytical, diagnostic and therapeutic context of Myc


  1. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Dews, M., Homayouni, A., Yu, D., Murphy, D., Sevignani, C., Wentzel, E., Furth, E.E., Lee, W.M., Enders, G.H., Mendell, J.T., Thomas-Tikhonenko, A. Nat. Genet. (2006) [Pubmed]
  2. Hypertrophic growth in cardiac myocytes is mediated by Myc through a Cyclin D2-dependent pathway. Zhong, W., Mao, S., Tobis, S., Angelis, E., Jordan, M.C., Roos, K.P., Fishbein, M.C., de Alborán, I.M., MacLellan, W.R. EMBO J. (2006) [Pubmed]
  3. Expression of cyclins E1 and E2 during mouse development and in neoplasia. Geng, Y., Yu, Q., Whoriskey, W., Dick, F., Tsai, K.Y., Ford, H.L., Biswas, D.K., Pardee, A.B., Amati, B., Jacks, T., Richardson, A., Dyson, N., Sicinski, P. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  4. Cre/lox-regulated transgenic zebrafish model with conditional myc-induced T cell acute lymphoblastic leukemia. Langenau, D.M., Feng, H., Berghmans, S., Kanki, J.P., Kutok, J.L., Look, A.T. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  5. Bim is a suppressor of Myc-induced mouse B cell leukemia. Egle, A., Harris, A.W., Bouillet, P., Cory, S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  6. The 3' IgH locus control region is sufficient to deregulate a c-myc transgene and promote mature B cell malignancies with a predominant Burkitt-like phenotype. Truffinet, V., Pinaud, E., Cogné, N., Petit, B., Guglielmi, L., Cogné, M., Denizot, Y. J. Immunol. (2007) [Pubmed]
  7. Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Soucek, L., Lawlor, E.R., Soto, D., Shchors, K., Swigart, L.B., Evan, G.I. Nat. Med. (2007) [Pubmed]
  8. Synergistic interaction of transforming growth factor alpha and c-myc in mouse mammary and salivary gland tumorigenesis. Amundadottir, L.T., Johnson, M.D., Merlino, G., Smith, G.H., Dickson, R.B. Cell Growth Differ. (1995) [Pubmed]
  9. c-myc inhibition of MyoD and myogenin-initiated myogenic differentiation. Miner, J.H., Wold, B.J. Mol. Cell. Biol. (1991) [Pubmed]
  10. Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland. Horsley, V., O'Carroll, D., Tooze, R., Ohinata, Y., Saitou, M., Obukhanych, T., Nussenzweig, M., Tarakhovsky, A., Fuchs, E. Cell (2006) [Pubmed]
  11. Genome-wide prediction of mammalian enhancers based on analysis of transcription-factor binding affinity. Hallikas, O., Palin, K., Sinjushina, N., Rautiainen, R., Partanen, J., Ukkonen, E., Taipale, J. Cell (2006) [Pubmed]
  12. The ubiquitin ligase HectH9 regulates transcriptional activation by Myc and is essential for tumor cell proliferation. Adhikary, S., Marinoni, F., Hock, A., Hulleman, E., Popov, N., Beier, R., Bernard, S., Quarto, M., Capra, M., Goettig, S., Kogel, U., Scheffner, M., Helin, K., Eilers, M. Cell (2005) [Pubmed]
  13. Estradiol is trophic for colon cancer in mice: effect on ornithine decarboxylase and c-myc messenger RNA. Narayan, S., Rajakumar, G., Prouix, H., Singh, P. Gastroenterology (1992) [Pubmed]
  14. Phenobarbital promotes liver growth in c-myc/TGF-alpha transgenic mice by inducing hypertrophy and inhibiting apoptosis. Sanders, S., Thorgeirsson, S.S. Carcinogenesis (1999) [Pubmed]
  15. Mild hypoxia promotes survival and proliferation of SOD2-deficient astrocytes via c-Myc activation. Liu, J., Narasimhan, P., Lee, Y.S., Song, Y.S., Endo, H., Yu, F., Chan, P.H. J. Neurosci. (2006) [Pubmed]
  16. Effects of dietary omega3 and omega6 lipids and vitamin E on proliferative response, lymphoid cell subsets, production of cytokines by spleen cells, and splenic protein levels for cytokines and oncogenes in MRL/MpJ-lpr/lpr mice. Venkatraman, J.T., Chu, W.C. J. Nutr. Biochem. (1999) [Pubmed]
  17. Increased expression of c-myc and c-Ha-ras in dichloroacetate and trichloroacetate-induced liver tumors in B6C3F1 mice. Nelson, M.A., Sanchez, I.M., Bull, R.J., Sylvester, S.R. Toxicology (1990) [Pubmed]
  18. Myc and Ras collaborate in inducing accumulation of active cyclin E/Cdk2 and E2F. Leone, G., DeGregori, J., Sears, R., Jakoi, L., Nevins, J.R. Nature (1997) [Pubmed]
  19. Myc but not Fos rescue of PDGF signalling block caused by kinase-inactive Src. Barone, M.V., Courtneidge, S.A. Nature (1995) [Pubmed]
  20. Role of Mxi1 in ageing organ systems and the regulation of normal and neoplastic growth. Schreiber-Agus, N., Meng, Y., Hoang, T., Hou, H., Chen, K., Greenberg, R., Cordon-Cardo, C., Lee, H.W., DePinho, R.A. Nature (1998) [Pubmed]
  21. Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis. Eischen, C.M., Weber, J.D., Roussel, M.F., Sherr, C.J., Cleveland, J.L. Genes Dev. (1999) [Pubmed]
  22. Repression of p15INK4b expression by Myc through association with Miz-1. Staller, P., Peukert, K., Kiermaier, A., Seoane, J., Lukas, J., Karsunky, H., Möröy, T., Bartek, J., Massagué, J., Hänel, F., Eilers, M. Nat. Cell Biol. (2001) [Pubmed]
  23. Activation of cyclin-dependent kinases by Myc mediates induction of cyclin A, but not apoptosis. Rudolph, B., Saffrich, R., Zwicker, J., Henglein, B., Müller, R., Ansorge, W., Eilers, M. EMBO J. (1996) [Pubmed]
  24. Cdk2-dependent phosphorylation of p27 facilitates its Myc-induced release from cyclin E/cdk2 complexes. Müller, D., Bouchard, C., Rudolph, B., Steiner, P., Stuckmann, I., Saffrich, R., Ansorge, W., Huttner, W., Eilers, M. Oncogene (1997) [Pubmed]
  25. Perillyl alcohol induces c-Myc-dependent apoptosis in Bcr/Abl-transformed leukemia cells. Clark, S.S. Oncology (2006) [Pubmed]
  26. Rapid and selective enhancement of DNA binding activity of the transcription factor AP1 by systemic administration of N-methyl-D-aspartate in murine hippocampus. Yoneda, Y., Ogita, K. Neurochem. Int. (1994) [Pubmed]
  27. Induction of c-myc transcription by the v-Abl tyrosine kinase requires Ras, Raf1, and cyclin-dependent kinases. Zou, X., Rudchenko, S., Wong, K., Calame, K. Genes Dev. (1997) [Pubmed]
  28. Association of Myn, the murine homolog of max, with c-Myc stimulates methylation-sensitive DNA binding and ras cotransformation. Prendergast, G.C., Lawe, D., Ziff, E.B. Cell (1991) [Pubmed]
  29. Aberrant expression and regulation of hepatic epidermal growth factor receptor in a c-myc transgenic mouse model. Woitach, J.T., Conner, E.A., Wirth, P.J., Thorgeirsson, S.S. J. Cell. Biochem. (1997) [Pubmed]
  30. Characterization of the murine Nramp1 promoter: requirements for transactivation by Miz-1. Bowen, H., Lapham, A., Phillips, E., Yeung, I., Alter-Koltunoff, M., Levi, B.Z., Perry, V.H., Mann, D.A., Barton, C.H. J. Biol. Chem. (2003) [Pubmed]
  31. The Cdk1 complex plays a prime role in regulating N-myc phosphorylation and turnover in neural precursors. Sjostrom, S.K., Finn, G., Hahn, W.C., Rowitch, D.H., Kenney, A.M. Dev. Cell (2005) [Pubmed]
  32. c-myc expression and transformed phenotypes in hybrid clones between mouse plasmacytoma S194 cells and normal spleen cells or fibroblasts. Oikawa, T., Yuhki, Y., Kondoh, N., Abe, K., Yuhki, N., Ogiso, Y., Kuzumaki, N. Int. J. Cancer (1988) [Pubmed]
  33. Nucleolar Arf sequesters Mdm2 and activates p53. Weber, J.D., Taylor, L.J., Roussel, M.F., Sherr, C.J., Bar-Sagi, D. Nat. Cell Biol. (1999) [Pubmed]
  34. TGF beta 1 inhibits NF-kappa B/Rel activity inducing apoptosis of B cells: transcriptional activation of I kappa B alpha. Arsura, M., Wu, M., Sonenshein, G.E. Immunity (1996) [Pubmed]
  35. B cell growth is controlled by phosphatidylinosotol 3-kinase-dependent induction of Rel/NF-kappaB regulated c-myc transcription. Grumont, R.J., Strasser, A., Gerondakis, S. Mol. Cell (2002) [Pubmed]
  36. Absence of caspase-3 protects pancreatic {beta}-cells from c-Myc-induced apoptosis without leading to tumor formation. Radziszewska, A., Schroer, S.A., Choi, D., Tajmir, P., Radulovich, N., Ho, J.C., Wang, L., Liadis, N., Hakem, R., Tsao, M.S., Penn, L.Z., Evan, G.I., Woo, M. J. Biol. Chem. (2009) [Pubmed]
  37. Three distinct IL-2 signaling pathways mediated by bcl-2, c-myc, and lck cooperate in hematopoietic cell proliferation. Miyazaki, T., Liu, Z.J., Kawahara, A., Minami, Y., Yamada, K., Tsujimoto, Y., Barsoumian, E.L., Permutter, R.M., Taniguchi, T. Cell (1995) [Pubmed]
  38. Ha-ras and c-myc oncogene expression interferes with morphological and functional differentiation of mammary epithelial cells in single and double transgenic mice. Andres, A.C., van der Valk, M.A., Schönenberger, C.A., Flückiger, F., LeMeur, M., Gerlinger, P., Groner, B. Genes Dev. (1988) [Pubmed]
  39. The c-Myc target gene PRDX3 is required for mitochondrial homeostasis and neoplastic transformation. Wonsey, D.R., Zeller, K.I., Dang, C.V. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  40. c-Myc rapidly induces acute myeloid leukemia in mice without evidence of lymphoma-associated antiapoptotic mutations. Luo, H., Li, Q., O'Neal, J., Kreisel, F., Le Beau, M.M., Tomasson, M.H. Blood (2005) [Pubmed]
  41. Design and properties of a Myc derivative that efficiently homodimerizes. Soucek, L., Helmer-Citterich, M., Sacco, A., Jucker, R., Cesareni, G., Nasi, S. Oncogene (1998) [Pubmed]
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