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Gene Review

MYBL2  -  v-myb avian myeloblastosis viral oncogene...

Homo sapiens

Synonyms: B-MYB, B-Myb, BMYB, Myb-like protein 2, Myb-related protein B
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Disease relevance of MYBL2

  • Furthermore, the MYBL2 and STK15 have been significantly overexpressed in prostate metastases, allowing a clear distinction between localized tumors and metastases [1].
  • Recent reports suggest a casual correlation between EGFR and B-Myb expression in primary breast carcinomas [2].
  • We show in this report that the human myeloid leukemia cell line GFD8 is a useful model to compare the biological function of the structurally related c-Myb and B-Myb proto-oncogenes and to investigate the c-myb domains required for this function [3].

High impact information on MYBL2

  • LNA-1 transactivated an artificial promoter carrying the cell cycle transcription factor E2F DNA-binding sequences and also upregulated the cyclin E (CCNEI) promoter, but not the B-myb (MYBL2) promoter [4].
  • B-Myb plays an essential role in cell cycle progression, and activation by E7 is likely to contribute to the mitogenic activity of the viral oncoprotein [5].
  • Gene-expression signatures associated with loss of bmyb in zebrafish are also correlated with conserved signatures in human tumor samples, and down-regulation of the B-myb signature genes is associated with retention of p53 function [6].
  • Cotransfection experiments with p53 expression plasmids and expression plasmids encoding in-frame deletion mutations in B-myb coding sequences indicate that the DNA-binding domain of the B-Myb protein is required for this activity [7].
  • It has been shown previously that phosphorylation of B-Myb by cdk2/cyclin A enhances its transcriptional activity [8].

Biological context of MYBL2


Anatomical context of MYBL2

  • For example, in aortic smooth muscle cells B-Myb represses transcription of the alpha2(V) collagen gene [12].
  • MLE-15 cells, a cell line expressing SP-A mRNA, also expressed B-Myb [13].
  • In this study, we show that the promoter of the fibroblast growth factor-4 (FGF-4) gene is strongly activated by B-Myb in HeLa cells and it can serve as a novel diagnostic tool for assessing B-Myb activity [14].
  • However, B-Myb, a more widely-expressed Myb family member, caused topo IIalpha trans-activation in both HL-60 cells and HeLa epithelial cervical carcinoma cells [15].
  • Redundant functions of B-Myb and c-Myb in differentiating myeloid cells [3].

Associations of MYBL2 with chemical compounds


Physical interactions of MYBL2

  • The B-Myb-interacting region of p57(KIP2) mapped to the cyclin-binding domain [11].
  • We also show that the bromo and histone acetyltransferase domains of p300 are sufficient to interact with and acetylate B-Myb [14].
  • In conclusion, these results imply that TRP-1 is a mammalian thioredoxin and plays as a transcriptional repressor through direct binding to the transcription factor B-Myb [19].

Enzymatic interactions of MYBL2

  • Previous studies demonstrated that B-Myb was phosphorylated at the onset of S phase, suggesting that it could be due to cyclin-dependent kinases [16].

Regulatory relationships of MYBL2

  • In this study we examined the functions of B-Myb required to overcome G1 arrest in Saos-2 cells induced by the retinoblastoma-related p107 protein [20].
  • Expression of the B-Myb transcription factor is upregulated during late G1 phase of the cell cycle by an E2F-dependent transcriptional mechanism [21].
  • We here report that B-Myb activates the HSP70 promoter by a novel mechanism which involves the heat shock element (HSE) [22].
  • In addition, by employing full-length or deleted B-Myb cDNA construct, we found that B-Myb down-regulates the COL1A1 proximal promoter through its C-terminal domain [23].
  • In particular, NDP-alpha-MSH down-regulated expression of B-Myb and Myc, two oncogenes considered of paramount importance for cell proliferation and cancer [24].

Other interactions of MYBL2

  • This study defines a novel function of B-Myb and further suggests that the p107 N-terminus provides an interaction domain for transcription factors involved in cell cycle control [20].
  • Furthermore, the multiple nuclear localization signals are in at least two regions in the COOH-terminal half of B-Myb, and one of them is adjacent to a potential cdc2 kinase site [10].
  • Co-regulation of B-Myb expression by E2F1 and EGF receptor [2].
  • Here we show that ectopic expression of cyclin A causes a pronounced reduction of B-Myb protein level [25].
  • Six sites in B-Myb fulfil the requirements for recognition by Cdk2 [26].

Analytical, diagnostic and therapeutic context of MYBL2


  1. Multiple genes in human 20q13 chromosomal region are involved in an advanced prostate cancer xenograft. Bar-Shira, A., Pinthus, J.H., Rozovsky, U., Goldstein, M., Sellers, W.R., Yaron, Y., Eshhar, Z., Orr-Urtreger, A. Cancer Res. (2002) [Pubmed]
  2. Co-regulation of B-Myb expression by E2F1 and EGF receptor. Hanada, N., Lo, H.W., Day, C.P., Pan, Y., Nakajima, Y., Hung, M.C. Mol. Carcinog. (2006) [Pubmed]
  3. Redundant functions of B-Myb and c-Myb in differentiating myeloid cells. Golay, J., Broccoli, V., Borleri, G.M., Erba, E., Faretta, M., Basilico, L., Ying, G.G., Piccinini, G., Shapiro, L.H., Lovrić, J., Nawrath, M., Mölling, K., Rambaldi, A., Introna, M. Cell Growth Differ. (1997) [Pubmed]
  4. The latent nuclear antigen of Kaposi sarcoma-associated herpesvirus targets the retinoblastoma-E2F pathway and with the oncogene Hras transforms primary rat cells. Radkov, S.A., Kellam, P., Boshoff, C. Nat. Med. (2000) [Pubmed]
  5. HPV16 E7 oncoprotein deregulates B-myb expression: correlation with targeting of p107/E2F complexes. Lam, E.W., Morris, J.D., Davies, R., Crook, T., Watson, R.J., Vousden, K.H. EMBO J. (1994) [Pubmed]
  6. A zebrafish bmyb mutation causes genome instability and increased cancer susceptibility. Shepard, J.L., Amatruda, J.F., Stern, H.M., Subramanian, A., Finkelstein, D., Ziai, J., Finley, K.R., Pfaff, K.L., Hersey, C., Zhou, Y., Barut, B., Freedman, M., Lee, C., Spitsbergen, J., Neuberg, D., Weber, G., Golub, T.R., Glickman, J.N., Kutok, J.L., Aster, J.C., Zon, L.I. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  7. Constitutive expression of B-myb can bypass p53-induced Waf1/Cip1-mediated G1 arrest. Lin, D., Fiscella, M., O'Connor, P.M., Jackman, J., Chen, M., Luo, L.L., Sala, A., Travali, S., Appella, E., Mercer, W.E. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  8. The transcription factor B-Myb is maintained in an inhibited state in target cells through its interaction with the nuclear corepressors N-CoR and SMRT. Li, X., McDonnell, D.P. Mol. Cell. Biol. (2002) [Pubmed]
  9. Mybl2 (Bmyb) maps to mouse chromosome 2 and human chromosome 20q 13.1. Noben-Trauth, K., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Sonoda, G., Testa, J.R., Klempnauer, K.H. Genomics (1996) [Pubmed]
  10. Functional domains of the human B-myb gene product. Nakagoshi, H., Takemoto, Y., Ishii, S. J. Biol. Chem. (1993) [Pubmed]
  11. The cell cycle-regulated B-Myb transcription factor overcomes cyclin-dependent kinase inhibitory activity of p57(KIP2) by interacting with its cyclin-binding domain. Joaquin, M., Watson, R.J. J. Biol. Chem. (2003) [Pubmed]
  12. B-Myb repressor function is regulated by cyclin A phosphorylation and sequences within the C-terminal domain. Petrovas, C., Jeay, S., Lewis, R.E., Sonenshein, G.E. Oncogene (2003) [Pubmed]
  13. Transcriptional regulation of the murine surfactant protein-A gene by B-Myb. Bruno, M.D., Whitsett, J.A., Ross, G.F., Korfhagen, T.R. J. Biol. Chem. (1999) [Pubmed]
  14. Effects of B-Myb on gene transcription: phosphorylation-dependent activity ans acetylation by p300. Johnson, L.R., Johnson, T.K., Desler, M., Luster, T.A., Nowling, T., Lewis, R.E., Rizzino, A. J. Biol. Chem. (2002) [Pubmed]
  15. c-Myb trans-activates the human DNA topoisomerase IIalpha gene promoter. Brandt, T.L., Fraser, D.J., Leal, S., Halandras, P.M., Kroll, A.R., Kroll, D.J. J. Biol. Chem. (1997) [Pubmed]
  16. Phosphorylation of B-Myb regulates its transactivation potential and DNA binding. Johnson, T.K., Schweppe, R.E., Septer, J., Lewis, R.E. J. Biol. Chem. (1999) [Pubmed]
  17. c-Myb repression of c-erbB-2 transcription by direct binding to the c-erbB-2 promoter. Mizuguchi, G., Kanei-Ishii, C., Takahashi, T., Yasukawa, T., Nagase, T., Horikoshi, M., Yamamoto, T., Ishii, S. J. Biol. Chem. (1995) [Pubmed]
  18. The highly conserved DNA-binding domains of A-, B- and c-Myb differ with respect to DNA-binding, phosphorylation and redox properties. Bergholtz, S., Andersen , T.O., Andersson, K.B., Borrebaek, J., Lüscher, B., Gabrielsen, O.S. Nucleic Acids Res. (2001) [Pubmed]
  19. Expression of a thioredoxin-related protein-1 is induced by prostaglandin E(2). Kim, K.Y., Lee, J.W., Park, M.S., Jung, M.H., Jeon, G.A., Nam, M.J. Int. J. Cancer (2006) [Pubmed]
  20. B-Myb overcomes a p107-mediated cell proliferation block by interacting with an N-terminal domain of p107. Joaquin, M., Bessa, M., Saville, M.K., Watson, R.J. Oncogene (2002) [Pubmed]
  21. The cell-cycle regulated transcription factor B-Myb is phosphorylated by cyclin A/Cdk2 at sites that enhance its transactivation properties. Saville, M.K., Watson, R.J. Oncogene (1998) [Pubmed]
  22. B-Myb and cyclin D1 mediate heat shock element dependent activation of the human HSP70 promoter. Kamano, H., Klempnauer, K.H. Oncogene (1997) [Pubmed]
  23. B-Myb acts as a repressor of human COL1A1 collagen gene expression by interacting with Sp1 and CBF factors in scleroderma fibroblasts. Cicchillitti, L., Jimenez, S.A., Sala, A., Saitta, B. Biochem. J. (2004) [Pubmed]
  24. Change in gene expression profile induced by alpha-melanocyte stimulating hormone in a malignant mesothelioma cell line. Colombo, G., Sordi, A., Turcatti, F., Carlin, A., Rossi, C., Lonati, C., Santambrogio, L., Gatti, S., Catania, A. Cell. Mol. Biol. (Noisy-le-grand) (2006) [Pubmed]
  25. Degradation of B-Myb by ubiquitin-mediated proteolysis: involvement of the Cdc34-SCF(p45Skp2) pathway. Charrasse, S., Carena, I., Brondani, V., Klempnauer, K.H., Ferrari, S. Oncogene (2000) [Pubmed]
  26. Identification of cyclin A/Cdk2 phosphorylation sites in B-Myb. Bartsch, O., Horstmann, S., Toprak, K., Klempnauer, K.H., Ferrari, S. Eur. J. Biochem. (1999) [Pubmed]
  27. Prognosis and gene expression profiling of 20q13-amplified breast cancers. Ginestier, C., Cervera, N., Finetti, P., Esteyries, S., Esterni, B., Adélaïde, J., Xerri, L., Viens, P., Jacquemier, J., Charafe-Jauffret, E., Chaffanet, M., Birnbaum, D., Bertucci, F. Clin. Cancer Res. (2006) [Pubmed]
  28. Myb binding sites mediate negative regulation of c-myb expression in T-cell lines. Guerra, J., Withers, D.A., Boxer, L.M. Blood (1995) [Pubmed]
  29. B-myb proto-oncogene products interact in vivo with each other via the carboxy-terminal conserved region. Kim, T., Jung, H., Min, S., Kim, K.T., Ha, H. FEBS Lett. (1999) [Pubmed]
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