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Gene Review

Myb  -  myeloblastosis oncogene

Mus musculus

Synonyms: AI550390, M16449, Proto-oncogene c-Myb, Transcriptional activator Myb, c-myb
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Disease relevance of Myb


High impact information on Myb

  • A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis [6].
  • To better understand its normal biological function, we have altered the c-myb gene by homologous recombination in mouse embryonic stem cells [6].
  • Analysis indicated that embryonic erythropoiesis, which occurs in the yolk sac, was not impaired by the c-myb alteration [6].
  • Resulting homozygous c-myb mutant mice displayed an interesting phenotype [6].
  • At day 13 of gestation these mice appeared normal, suggesting that c-myb is not essential for early development [6].

Chemical compound and disease context of Myb


Biological context of Myb

  • The down-regulation of Myb by Wnt-1 signal may play an important role in a variety of developmental steps [12].
  • We show that Myb is required to protect activated peripheral T cells from bcl-2-independent apoptosis and that overexpression of oncogenic v-Myb is antiapoptotic [13].
  • Differential regulation of c-Myb-induced transcription activation by a phosphorylation site in the negative regulatory domain [2].
  • Consistent with the established roles of c-Myb and Runx factors in Edelta function, we detected low level, enhancer-independent activity of the Ddelta2 promoter in transient transfection experiments [14].
  • This suggests that phosphorylation of serine 528 may differentially regulate c-Myb activity at different promoters [2].

Anatomical context of Myb

  • To investigate the possibility that this regulatory connection contributes to Myb's oncogenicity, we expressed a dominant negative Myb in the myeloid leukemic cell line RI-4-11 [4].
  • Here we have studied the mechanism of action and the nature of target genes through which c-Myb mediates the block in differentiation of 32Dcl3 murine myeloid cells [15].
  • Interestingly, c-myb mRNA and Myb protein are expressed at levels similar to the levels observed in myeloid progenitor cells, but are not overexpressed [16].
  • The differentiation into erythrocytes was accompanied by sequential transient expression of the proto-oncogenes in the order of c-fos, c-myb, c-myc and c-k-ras, during the first 48 hr of differentiation induction [17].
  • To compare the biological activities of c-myb and B-myb, the two genes were overexpressed in 32Dcl3 cells, which are known to undergo terminal differentiation into granulocytes in the presence of granulocyte colony-stimulating factor (G-CSF) [18].

Associations of Myb with chemical compounds

  • We have tested the ability of S528A Myb to transactivate a series of cellular target promoters and report that the serine to alanine substitution increased the ability of Myb to activate transcription from the CD34 promoter but not the c-myc or mim-1 promoters [2].
  • While bcl-2 expression was reduced by 50% in ERMYB cells grown in the absence of beta-estradiol, there was no increase in DNA laddering, suggesting that Myb was not protecting ERMYB cells from apoptosis [19].
  • Activation of Myb/ER in F-MEL cells had no effect upon the early and transient inhibition of entry into S phase associated with dimethyl sulfoxide (DMSO) induction [20].
  • Dexamethasone, which blocks expression of HMBA-induced MELC differentiation, does not alter the early pattern of changes in protooncogene mRNA nor the sustained elevation of c-fos, but it does inhibit the continued suppression of c-myb allowing c-myb to return toward control levels [21].
  • These results suggest that the two isoforms of c-Myb differentially regulate apoptotic death of myeloid cells through differential regulation of glutathione S-transferase micro gene expression [22].

Physical interactions of Myb

  • Here we report that TIF1beta directly binds to the NRD and negatively regulates the c-Myb-dependent trans-activation [23].
  • Sequence analysis of the 5' flanking region of the c-myb gene revealed a consensus PU box at position +16 to +21 able to specifically interact in electrophoretic mobility shift assays with either bacterially synthesized PU.1 protein or whole cell extracts from differentiated 32Dcl3 cells [24].
  • A segment of the bcl-2 promoter (nucleotides +34 to +58 relative to the transcription initiation site) contained a putative Myb-binding site and was shown to specifically interact with B-Myb and to confer B-Myb responsiveness to a bcl-2/chloramphenicol acetyltransferase reporter construct [25].
  • Here we have determined that Myb-related transcription factors bind to the gamma 3 site and appear to be critical for the full activity of the TCR-gamma enhancer. c-myb products can transactivate the gamma 3 site in cell lines that do not ordinarily support enhancer activity of the gamma 3 site [26].
  • Myb binding sites within the N-ras promoter repress transcription [27].

Regulatory relationships of Myb

  • We observed that c-myb blocked the G-CSF-induced terminal differentiation of 32Dcl3 cells, resulting in their continued proliferation in the presence of G-CSF [18].
  • Enforced c-myb expression also prevents the loss in leukemogenicity of M1 cells normally induced by interleukin-6 or leukemia inhibitory factor [28].
  • Calcineurin mediates repression of plasma membrane Ca2+-ATPase-4 (PMCA4) expression in neurons, whereas c-Myb is known to repress PMCA1 expression in vascular smooth muscle cells (VSMC) [29].
  • Ectopic overexpression of the glutathione S-transferase micro gene in 32Dcl3 cells resulted in protection of cells from interleukin-3 withdrawal-induced cell death similar to that seen with the ectopic overexpression of p89 c-Myb [22].
  • IL-4 did not significantly affect LIF-induced junB expression or suppression of c-myb expression [30].

Other interactions of Myb


Analytical, diagnostic and therapeutic context of Myb


  1. A transcription-factor-binding surface of coactivator p300 is required for haematopoiesis. Kasper, L.H., Boussouar, F., Ney, P.A., Jackson, C.W., Rehg, J., van Deursen, J.M., Brindle, P.K. Nature (2002) [Pubmed]
  2. Differential regulation of c-Myb-induced transcription activation by a phosphorylation site in the negative regulatory domain. Miglarese, M.R., Richardson, A.F., Aziz, N., Bender, T.P. J. Biol. Chem. (1996) [Pubmed]
  3. A Myb dependent pathway maintains Friend murine erythroleukemia cells in an immature and proliferating state. Chen, J., Kremer, C.S., Bender, T.P. Oncogene (2002) [Pubmed]
  4. Regulation of the resident chromosomal copy of c-myc by c-Myb is involved in myeloid leukemogenesis. Schmidt, M., Nazarov, V., Stevens, L., Watson, R., Wolff, L. Mol. Cell. Biol. (2000) [Pubmed]
  5. Cooperation of Myb and Myc proteins in T cell lymphomagenesis. Davies, J., Badiani, P., Weston, K. Oncogene (1999) [Pubmed]
  6. A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis. Mucenski, M.L., McLain, K., Kier, A.B., Swerdlow, S.H., Schreiner, C.M., Miller, T.A., Pietryga, D.W., Scott, W.J., Potter, S.S. Cell (1991) [Pubmed]
  7. Protooncogene expression in normal, preleukemic, and leukemic murine erythroid cells and its relationship to differentiation and proliferation. Robert-Lézénès, J., Meneceur, P., Ray, D., Moreau-Gachelin, F. Cancer Res. (1988) [Pubmed]
  8. Calcium ionophore-induced transient down-regulation of c-myb mRNA levels in Friend erythroleukemia cells. Schaefer, A., Stöcker, U., Marquardt, H. J. Biol. Chem. (1993) [Pubmed]
  9. c-myb effects on kinetic events during MEL cell differentiation. Danish, R., el-Awar, O., Weber, B.L., Langmore, J., Turka, L.A., Ryan, J.J., Clarke, M.F. Oncogene (1992) [Pubmed]
  10. Modulation of the c-myb, c-myc and p53 mRNA and protein levels during induced murine erythroleukemia cell differentiation. Richon, V.M., Ramsay, R.G., Rifkind, R.A., Marks, P.A. Oncogene (1989) [Pubmed]
  11. Nitric oxide-releasing agents and cGMP analogues inhibit murine erythroleukemia cell differentiation and suppress erythroid-specific gene expression: correlation with decreased DNA binding of NF-E2 and altered c-myb mRNA expression. Suhasini, M., Boss, G.R., Pascual, F.E., Pilz, R.B. Cell Growth Differ. (1995) [Pubmed]
  12. Wnt-1 signal induces phosphorylation and degradation of c-Myb protein via TAK1, HIPK2, and NLK. Kanei-Ishii, C., Ninomiya-Tsuji, J., Tanikawa, J., Nomura, T., Ishitani, T., Kishida, S., Kokura, K., Kurahashi, T., Ichikawa-Iwata, E., Kim, Y., Matsumoto, K., Ishii, S. Genes Dev. (2004) [Pubmed]
  13. c-Myb transcription is activated by protein kinase B (PKB) following interleukin 2 stimulation of Tcells and is required for PKB-mediated protection from apoptosis. Lauder, A., Castellanos, A., Weston, K. Mol. Cell. Biol. (2001) [Pubmed]
  14. Regulation of the murine Ddelta2 promoter by upstream stimulatory factor 1, Runx1, and c-Myb. Carabana, J., Ortigoza, E., Krangel, M.S. J. Immunol. (2005) [Pubmed]
  15. c-Myc is essential but not sufficient for c-Myb-mediated block of granulocytic differentiation. Kumar, A., Lee, C.M., Reddy, E.P. J. Biol. Chem. (2003) [Pubmed]
  16. Mml1, a new common integration site in murine leukemia virus-induced promonocytic leukemias maps to mouse chromosome 10. Koller, R., Krall, M., Mock, B., Bies, J., Nazarov, V., Wolff, L. Virology (1996) [Pubmed]
  17. Sequential expression of proto-oncogenes during a mouse erythroleukemia cell differentiation. Todokoro, K., Ikawa, Y. Biochem. Biophys. Res. Commun. (1986) [Pubmed]
  18. The C-terminal domain of B-Myb acts as a positive regulator of transcription and modulates its biological functions. Oh, I.H., Reddy, E.P. Mol. Cell. Biol. (1998) [Pubmed]
  19. Inactivation of a c-Myb/estrogen receptor fusion protein in transformed primary cells leads to granulocyte/macrophage differentiation and down regulation of c-kit but not c-myc or cdc2. Hogg, A., Schirm, S., Nakagoshi, H., Bartley, P., Ishii, S., Bishop, J.M., Gonda, T.J. Oncogene (1997) [Pubmed]
  20. Conditional inhibition of erythroid differentiation by c-Myb/oestrogen receptor fusion proteins. Lyon, J.J., Watson, R.J. Differentiation (1995) [Pubmed]
  21. Changes in gene expression associated with induced differentiation of erythroleukemia: protooncogenes, globin genes, and cell division. Ramsay, R.G., Ikeda, K., Rifkind, R.A., Marks, P.A. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  22. Molecular mechanisms associated with the regulation of apoptosis by the two alternatively spliced products of c-Myb. Kumar, A., Baker, S.J., Lee, C.M., Reddy, E.P. Mol. Cell. Biol. (2003) [Pubmed]
  23. Oncogenic activation of c-Myb correlates with a loss of negative regulation by TIF1beta and Ski. Nomura, T., Tanikawa, J., Akimaru, H., Kanei-Ishii, C., Ichikawa-Iwata, E., Khan, M.M., Ito, H., Ishii, S. J. Biol. Chem. (2004) [Pubmed]
  24. Granulocytic differentiation of normal hematopoietic precursor cells induced by transcription factor PU.1 correlates with negative regulation of the c-myb promoter. Bellon, T., Perrotti, D., Calabretta, B. Blood (1997) [Pubmed]
  25. Resistance to apoptosis in CTLL-2 cells overexpressing B-Myb is associated with B-Myb-dependent bcl-2 induction. Grassilli, E., Salomoni, P., Perrotti, D., Franceschi, C., Calabretta, B. Cancer Res. (1999) [Pubmed]
  26. The role of c-Myb or a related factor in regulating the T cell receptor gamma gene enhancer. Hsiang, Y.H., Goldman, J.P., Raulet, D.H. J. Immunol. (1995) [Pubmed]
  27. Myb binding sites within the N-ras promoter repress transcription. Ganter, B., Lipsick, J.S. Oncogene (1997) [Pubmed]
  28. Deregulated c-myb disrupts interleukin-6- or leukemia inhibitory factor-induced myeloid differentiation prior to c-myc: role in leukemogenesis. Selvakumaran, M., Liebermann, D.A., Hoffman-Liebermann, B. Mol. Cell. Biol. (1992) [Pubmed]
  29. Calcineurin-independent regulation of plasma membrane Ca2+ ATPase-4 in the vascular smooth muscle cell cycle. Afroze, T., Yang, L.L., Wang, C., Gros, R., Kalair, W., Hoque, A.N., Mungrue, I.N., Zhu, Z., Husain, M. Am. J. Physiol., Cell Physiol. (2003) [Pubmed]
  30. Inhibition by interleukin 4 of leukemia inhibitory factor-, interleukin 6-, and dexamethasone-induced differentiation of mouse myeloid leukemia cells: role of c-myc and junB proto-oncogenes. Kasukabe, T., Okabe-Kado, J., Hozumi, M., Honma, Y. Cancer Res. (1994) [Pubmed]
  31. Chromosome assignments of four mouse cellular homologs of sarcoma and leukemia virus oncogenes. Sakaguchi, A.Y., Lalley, P.A., Zabel, B.U., Ellis, R.W., Scolnick, E.M., Naylor, S.L. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  32. Members of the nuclear factor kappa B family transactivate the murine c-myb gene. Toth, C.R., Hostutler, R.F., Baldwin, A.S., Bender, T.P. J. Biol. Chem. (1995) [Pubmed]
  33. c-Myb regulates lineage choice in developing thymocytes via its target gene Gata3. Maurice, D., Hooper, J., Lang, G., Weston, K. EMBO J. (2007) [Pubmed]
  34. Myb and ets proteins are candidate regulators of c-kit expression in human hematopoietic cells. Ratajczak, M.Z., Perrotti, D., Melotti, P., Powzaniuk, M., Calabretta, B., Onodera, K., Kregenow, D.A., Machalinski, B., Gewirtz, A.M. Blood (1998) [Pubmed]
  35. Molecular cloning reveals that the p160 Myb-binding protein is a novel, predominantly nucleolar protein which may play a role in transactivation by Myb. Tavner, F.J., Simpson, R., Tashiro, S., Favier, D., Jenkins, N.A., Gilbert, D.J., Copeland, N.G., Macmillan, E.M., Lutwyche, J., Keough, R.A., Ishii, S., Gonda, T.J. Mol. Cell. Biol. (1998) [Pubmed]
  36. Functional analysis of the c-myb proto-oncogene. Lin, H.H., Sternfeld, D.C., Shinpock, S.G., Popp, R.A., Mucenski, M.L. Curr. Top. Microbiol. Immunol. (1996) [Pubmed]
  37. Mechanism of c-Myb-C/EBP beta cooperation from separated sites on a promoter. Tahirov, T.H., Sato, K., Ichikawa-Iwata, E., Sasaki, M., Inoue-Bungo, T., Shiina, M., Kimura, K., Takata, S., Fujikawa, A., Morii, H., Kumasaka, T., Yamamoto, M., Ishii, S., Ogata, K. Cell (2002) [Pubmed]
  38. Anomalous megakaryocytopoiesis in mice with mutations in the c-Myb gene. Metcalf, D., Carpinelli, M.R., Hyland, C., Mifsud, S., Dirago, L., Nicola, N.A., Hilton, D.J., Alexander, W.S. Blood (2005) [Pubmed]
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