Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1997 Mar 17;16(6):1371–1380. doi: 10.1093/emboj/16.6.1371

tom-1, a novel v-Myb target gene expressed in AMV- and E26-transformed myelomonocytic cells.

O Burk 1, S Worpenberg 1, B Haenig 1, K H Klempnauer 1
PMCID: PMC1169734  PMID: 9135152

Abstract

The retroviral oncogene v-myb is a mutated and truncated version of the c-myb proto-oncogene and encodes a transcription factor (v-Myb) that specifically transforms myelomonocytic cells. Two different variants of v-myb, transduced independently by the oncogenic chicken retroviruses AMV and E26, have been characterized. It is believed that both variants of v-Myb transform myelomonocytic cells by affecting the expression of specific genes; however, no target genes common to both oncogenic viruses have been identified. Here, we describe the identification of a novel v-Myb target gene, designated as tom-1 (target of myb 1). The tom-1 gene has two promoters, one of which is Myb-inducible. tom-1 is expressed at elevated levels in AMV-transformed as well as in E26-transformed myeloid cells. We show that tom-1 activation by v-Myb does not require de novo protein synthesis and that the Myb-inducible tom-1 promoter contains a functional Myb binding site. Thus, tom-1 is the first example of a direct target gene for both oncogenic forms of the v-myb gene. Further analysis of the Myb-inducible tom-1 promoter shows that a C/EBP binding site is juxtaposed to the Myb binding site and that C/EBP is required for the Myb-dependent activation of the promoter. Together with previous work our results suggest that C/EBP may be a general cooperation partner for v-Myb in myelomonocytic cells.

Full Text

The Full Text of this article is available as a PDF (445.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams M. D., Soares M. B., Kerlavage A. R., Fields C., Venter J. C. Rapid cDNA sequencing (expressed sequence tags) from a directionally cloned human infant brain cDNA library. Nat Genet. 1993 Aug;4(4):373–380. doi: 10.1038/ng0893-373. [DOI] [PubMed] [Google Scholar]
  2. Biedenkapp H., Borgmeyer U., Sippel A. E., Klempnauer K. H. Viral myb oncogene encodes a sequence-specific DNA-binding activity. Nature. 1988 Oct 27;335(6193):835–837. doi: 10.1038/335835a0. [DOI] [PubMed] [Google Scholar]
  3. Burk O., Mink S., Ringwald M., Klempnauer K. H. Synergistic activation of the chicken mim-1 gene by v-myb and C/EBP transcription factors. EMBO J. 1993 May;12(5):2027–2038. doi: 10.1002/j.1460-2075.1993.tb05852.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  5. Dai P., Akimaru H., Tanaka Y., Hou D. X., Yasukawa T., Kanei-Ishii C., Takahashi T., Ishii S. CBP as a transcriptional coactivator of c-Myb. Genes Dev. 1996 Mar 1;10(5):528–540. doi: 10.1101/gad.10.5.528. [DOI] [PubMed] [Google Scholar]
  6. Desbiens X., Quéva C., Jaffredo T., Stéhelin D., Vandenbunder B. The relationship between cell proliferation and the transcription of the nuclear oncogenes c-myc, c-myb and c-ets-1 during feather morphogenesis in the chick embryo. Development. 1991 Mar;111(3):699–713. doi: 10.1242/dev.111.3.699. [DOI] [PubMed] [Google Scholar]
  7. Graf T. Myb: a transcriptional activator linking proliferation and differentiation in hematopoietic cells. Curr Opin Genet Dev. 1992 Apr;2(2):249–255. doi: 10.1016/s0959-437x(05)80281-3. [DOI] [PubMed] [Google Scholar]
  8. Ibanez C. E., Lipsick J. S. trans activation of gene expression by v-myb. Mol Cell Biol. 1990 May;10(5):2285–2293. doi: 10.1128/mcb.10.5.2285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Introna M., Golay J., Frampton J., Nakano T., Ness S. A., Graf T. Mutations in v-myb alter the differentiation of myelomonocytic cells transformed by the oncogene. Cell. 1990 Dec 21;63(6):1289–1297. doi: 10.1016/0092-8674(90)90424-d. [DOI] [PubMed] [Google Scholar]
  10. Klempnauer K. H., Arnold H., Biedenkapp H. Activation of transcription by v-myb: evidence for two different mechanisms. Genes Dev. 1989 Oct;3(10):1582–1589. doi: 10.1101/gad.3.10.1582. [DOI] [PubMed] [Google Scholar]
  11. Klempnauer K. H., Gonda T. J., Bishop J. M. Nucleotide sequence of the retroviral leukemia gene v-myb and its cellular progenitor c-myb: the architecture of a transduced oncogene. Cell. 1982 Dec;31(2 Pt 1):453–463. doi: 10.1016/0092-8674(82)90138-6. [DOI] [PubMed] [Google Scholar]
  12. Klempnauer K. H., Ramsay G., Bishop J. M., Moscovici M. G., Moscovici C., McGrath J. P., Levinson A. D. The product of the retroviral transforming gene v-myb is a truncated version of the protein encoded by the cellular oncogene c-myb. Cell. 1983 Jun;33(2):345–355. doi: 10.1016/0092-8674(83)90416-6. [DOI] [PubMed] [Google Scholar]
  13. Kulessa H., Frampton J., Graf T. GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and erythroblasts. Genes Dev. 1995 May 15;9(10):1250–1262. doi: 10.1101/gad.9.10.1250. [DOI] [PubMed] [Google Scholar]
  14. Lane T., Ibanez C., Garcia A., Graf T., Lipsick J. Transformation by v-myb correlates with trans-activation of gene expression. Mol Cell Biol. 1990 Jun;10(6):2591–2598. doi: 10.1128/mcb.10.6.2591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Leonard M. W., Lim K. C., Engel J. D. Expression of the chicken GATA factor family during early erythroid development and differentiation. Development. 1993 Oct;119(2):519–531. doi: 10.1242/dev.119.2.519. [DOI] [PubMed] [Google Scholar]
  16. Liang P., Averboukh L., Pardee A. B. Distribution and cloning of eukaryotic mRNAs by means of differential display: refinements and optimization. Nucleic Acids Res. 1993 Jul 11;21(14):3269–3275. doi: 10.1093/nar/21.14.3269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Liang P., Pardee A. B. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science. 1992 Aug 14;257(5072):967–971. doi: 10.1126/science.1354393. [DOI] [PubMed] [Google Scholar]
  18. Metz T., Graf T. v-myb and v-ets transform chicken erythroid cells and cooperate both in trans and in cis to induce distinct differentiation phenotypes. Genes Dev. 1991 Mar;5(3):369–380. doi: 10.1101/gad.5.3.369. [DOI] [PubMed] [Google Scholar]
  19. Moscovici C., Moscovici M. G., Jimenez H., Lai M. M., Hayman M. J., Vogt P. K. Continuous tissue culture cell lines derived from chemically induced tumors of Japanese quail. Cell. 1977 May;11(1):95–103. doi: 10.1016/0092-8674(77)90320-8. [DOI] [PubMed] [Google Scholar]
  20. Mucenski M. L., McLain K., Kier A. B., Swerdlow S. H., Schreiner C. M., Miller T. A., Pietryga D. W., Scott W. J., Jr, Potter S. S. A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis. Cell. 1991 May 17;65(4):677–689. doi: 10.1016/0092-8674(91)90099-k. [DOI] [PubMed] [Google Scholar]
  21. Ness S. A., Marknell A., Graf T. The v-myb oncogene product binds to and activates the promyelocyte-specific mim-1 gene. Cell. 1989 Dec 22;59(6):1115–1125. doi: 10.1016/0092-8674(89)90767-8. [DOI] [PubMed] [Google Scholar]
  22. Plaza S., Turque N., Dozier C., Bailly M., Saule S. C-Myb acts as transcriptional activator of the quail PAX6 (PAX-QNR) promoter through two different mechanisms. Oncogene. 1995 Jan 19;10(2):329–340. [PubMed] [Google Scholar]
  23. Scott L. M., Civin C. I., Rorth P., Friedman A. D. A novel temporal expression pattern of three C/EBP family members in differentiating myelomonocytic cells. Blood. 1992 Oct 1;80(7):1725–1735. [PubMed] [Google Scholar]
  24. Sitzmann J., Noben-Trauth K., Klempnauer K. H. Expression of mouse c-myb during embryonic development. Oncogene. 1995 Dec 7;11(11):2273–2279. [PubMed] [Google Scholar]
  25. Thiele C. J., McKeon C., Triche T. J., Ross R. A., Reynolds C. P., Israel M. A. Differential protooncogene expression characterizes histopathologically indistinguishable tumors of the peripheral nervous system. J Clin Invest. 1987 Sep;80(3):804–811. doi: 10.1172/JCI113137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Trüeb B., Schreier T., Winterhalter K. H., Strehler E. E. Sequence of a cDNA clone encoding chicken ribosomal protein S17. Nucleic Acids Res. 1988 May 25;16(10):4723–4723. doi: 10.1093/nar/16.10.4723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Weston K., Bishop J. M. Transcriptional activation by the v-myb oncogene and its cellular progenitor, c-myb. Cell. 1989 Jul 14;58(1):85–93. doi: 10.1016/0092-8674(89)90405-4. [DOI] [PubMed] [Google Scholar]
  28. Yeh W. C., Cao Z., Classon M., McKnight S. L. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes Dev. 1995 Jan 15;9(2):168–181. doi: 10.1101/gad.9.2.168. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES