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Gene Review

Myb  -  Myb oncogene-like

Drosophila melanogaster

Synonyms: CG9045, D-myb, DMyb, Dm Myb, Dm myb, ...
 
 
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Disease relevance of Myb

 

High impact information on Myb

  • These complexes contain RBF, E2F, and Myb-interacting proteins that have previously been shown to control developmentally regulated patterns of DNA replication in follicle cells [4].
  • The DNA-binding region of Myb consists of three imperfect tandem repeats (R1, R2, and R3) [5].
  • A Drosophila Myb binding site, as well as the binding site for another Myb complex member (p120), is necessary in cis for replication of reporter transgenes [6].
  • Role for a Drosophila Myb-containing protein complex in site-specific DNA replication [6].
  • Together, these data support a model in which DmMyb activates a repressive complex containing Mip130 into a complex competent to support replication at specific loci in a temporally and developmentally proscribed manner [7].
 

Biological context of Myb

  • These results suggest that the absence of Drosophila Myb causes a defect in S phase that may result in M-phase abnormalities [1].
  • Drosophila melanogaster possesses a single gene, Dm myb, that is closely related to the vertebrate family of Myb genes, which encode transcription factors involved in regulatory decisions affecting cell proliferation, differentiation and apoptosis [8].
  • Genetic interaction analysis reveals that these genes work together to promote mitosis, thereby demonstrating the physiological relevance of the biochemical interaction between the Myb and CBP proteins within a developing organism [8].
  • RNA interference (RNAi) to selectively remove each DmMyb complex member revealed that DmMyb protein levels are dependent upon the presence of several of the complex members [7].
  • Vertebrate c-Myb is a key regulator of the G(1)/S transition in cell cycle, while Drosophila Myb (dMyb) is important for the G(2)/M transition [9].
 

Anatomical context of Myb

 

Associations of Myb with chemical compounds

  • The Drosophila Myb homologue retains an evolutionarily conserved typical sequence of three imperfect tandem tryptophan repeat units (R1-R2-R3) of 51-53 amino acids towards its N-terminus as its presumptive DNA binding domain [2].
  • Co-transfection experiments in NIH 3T3 fibroblasts showed that the resulting chimeric protein, Myb/En/ER, repressed transactivation of a c-Myb-responsive reporter only in the presence of the synthetic steroid, 4-hydroxytamoxifen (OHT) [15].
  • The DNA-binding domain of Drosophila c-Myb protein has been studied using different spectroscopic probes, namely CD, fluorescence, acrylamide quenching and NMR, to determine the structure of some of its sub-domains and their relative stabilities in aqueous solutions [16].
 

Physical interactions of Myb

  • Characterization of the extended Myb-like DNA-binding domain of trithorax group protein Zeste [17].
  • The complete amino acid sequence of Adf-1 deduced from the longest cDNA reveals structural similarities to the putative helix-turn-helix DNA binding motif of Myb and Myb-related proteins [18].
 

Regulatory relationships of Myb

 

Other interactions of Myb

  • This suggests that Mip130 activity without DmMyb counteraction may be responsible for the Dm-myb mutant lethality [7].
  • MYB and CBP: physiological relevance of a biochemical interaction [8].
  • Consistent with a role for Drosophila Myb during S phase, we detected Dm-Myb protein in S-phase nuclei of wild-type mitotic cells as well as endocycling cells, which lack both an M phase and cyclin B expression [1].
  • These and other data now link together the Myb and E2F2 complexes in higher-order assembly to specific chromosomal sites for the regulation of transcription [19].
  • Identification of a Drosophila Myb-E2F2/RBF transcriptional repressor complex [19].
 

Analytical, diagnostic and therapeutic context of Myb

  • To further understand biochemically the functions of the Myb complex, we fractionated Drosophila embryo extracts relying upon affinity chromatography [19].

References

  1. Mutation of the Drosophila homologue of the Myb protooncogene causes genomic instability. Manak, J.R., Mitiku, N., Lipsick, J.S. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  2. Bacterial expression, characterization and DNA binding studies on Drosophila melanogaster c-Myb DNA-binding protein. Madan, A., Radha, P.K., Hosur, R.V., Padhy, L.C. Eur. J. Biochem. (1995) [Pubmed]
  3. Definition of a consensus sequence for peptide substrate recognition by p44mpk, the meiosis-activated myelin basic protein kinase. Clark-Lewis, I., Sanghera, J.S., Pelech, S.L. J. Biol. Chem. (1991) [Pubmed]
  4. Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes. Korenjak, M., Taylor-Harding, B., Binné, U.K., Satterlee, J.S., Stevaux, O., Aasland, R., White-Cooper, H., Dyson, N., Brehm, A. Cell (2004) [Pubmed]
  5. Solution structure of a specific DNA complex of the Myb DNA-binding domain with cooperative recognition helices. Ogata, K., Morikawa, S., Nakamura, H., Sekikawa, A., Inoue, T., Kanai, H., Sarai, A., Ishii, S., Nishimura, Y. Cell (1994) [Pubmed]
  6. Role for a Drosophila Myb-containing protein complex in site-specific DNA replication. Beall, E.L., Manak, J.R., Zhou, S., Bell, M., Lipsick, J.S., Botchan, M.R. Nature (2002) [Pubmed]
  7. Dm-myb mutant lethality in Drosophila is dependent upon mip130: positive and negative regulation of DNA replication. Beall, E.L., Bell, M., Georlette, D., Botchan, M.R. Genes Dev. (2004) [Pubmed]
  8. MYB and CBP: physiological relevance of a biochemical interaction. Fung, S.M., Ramsay, G., Katzen, A.L. Mech. Dev. (2003) [Pubmed]
  9. Myb controls G(2)/M progression by inducing cyclin B expression in the Drosophila eye imaginal disc. Okada, M., Akimaru, H., Hou, D.X., Takahashi, T., Ishii, S. EMBO J. (2002) [Pubmed]
  10. The Drosophila stonewall gene encodes a putative transcription factor essential for germ cell development. Clark, K.A., McKearin, D.M. Development (1996) [Pubmed]
  11. Functional evolution of the vertebrate Myb gene family: B-Myb, but neither A-Myb nor c-Myb, complements Drosophila Myb in hemocytes. Davidson, C.J., Tirouvanziam, R., Herzenberg, L.A., Lipsick, J.S. Genetics (2005) [Pubmed]
  12. Dominant interfering alleles define a role for c-Myb in T-cell development. Badiani, P., Corbella, P., Kioussis, D., Marvel, J., Weston, K. Genes Dev. (1994) [Pubmed]
  13. c-Myb-dependent cell cycle progression and Ca2+ storage in cultured vascular smooth muscle cells. Husain, M., Bein, K., Jiang, L., Alper, S.L., Simons, M., Rosenberg, R.D. Circ. Res. (1997) [Pubmed]
  14. c-Myb function in fibroblasts. Bein, K., Husain, M., Ware, J.A., Mucenski, M.L., Rosenberg, R.D., Simons, M. J. Cell. Physiol. (1997) [Pubmed]
  15. Interference of Myb transactivation activity by a conditional dominant negative protein: functional interference in a cytotoxic T-cell line results in G1 arrest. Lyon, J.J., Watson, R.J. Gene (1996) [Pubmed]
  16. The DNA-binding domain of Drosophila melanogaster c-Myb undergoes a multistate denaturation. Madan, A., Radha, P.K., Srivastava, A., Padhy, L.C., Hosur, R.V. Eur. J. Biochem. (1995) [Pubmed]
  17. Characterization of the extended Myb-like DNA-binding domain of trithorax group protein Zeste. Mohrmann, L., Kal, A.J., Verrijzer, C.P. J. Biol. Chem. (2002) [Pubmed]
  18. Cloning of Drosophila transcription factor Adf-1 reveals homology to Myb oncoproteins. England, B.P., Admon, A., Tjian, R. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  19. Identification of a Drosophila Myb-E2F2/RBF transcriptional repressor complex. Lewis, P.W., Beall, E.L., Fleischer, T.C., Georlette, D., Link, A.J., Botchan, M.R. Genes Dev. (2004) [Pubmed]
 
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