Myb and Ets proteins cooperate in transcriptional activation of the mim-1 promoter.
Abstract
In the generation of the acutely transforming avian retrovirus E26, both myb and ets genes have been transduced, leading to the production of a Gag-Myb-Ets fusion protein. This co-occurrence of v-myb and v-ets oncogenes suggests that the two might have a functional relationship. To look for such a relationship, we tested the transcriptional activation activity of Myb alone or with coexpressed Ets-1 or Ets-2. Using the promoter of the v-Myb-inducible mim-1 gene as a target, we found that full-length c-Myb gene products were poor activators of transcription, while an oncogenic (truncated) form of this protein was a strong trans-activator. However, coexpression of Ets-2 with full-length or truncated forms of Myb greatly increased trans-activation. Coexpression of Ets-1, Fos, Jun, or Myc with Myb did not increase trans-activation of the mim-1 promoter. The ability of Myb and Ets-2 to transactivate was cooperative, since Ets-2 alone gave little or no activation. Bacterially synthesized Ets-2 protein was found to bind specifically to the mim-1 promoter, suggesting that it may be a target for both Myb and Ets proteins. Thus, Myb and Ets proteins can cooperate in transcriptional activation, and their co-occurrence in the E26 virus may reflect a functional relationship between these two oncoproteins. Truncated forms of Myb may have a reduced need for cooperating factors such as Ets-2, and this might constitute an important mechanism associated with oncogenic activation.
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- Souza LM, Strommer JN, Hillyard RL, Komaromy MC, Baluda MA. Cellular sequences are present in the presumptive avian myeloblastosis virus genome. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5177–5181. [PMC free article] [PubMed] [Google Scholar]
- Rushlow KE, Lautenberger JA, Papas TS, Baluda MA, Perbal B, Chirikjian JG, Reddy EP. Nucleotide sequence of the transforming gene of avian myeloblastosis virus. Science. 1982 Jun 25;216(4553):1421–1423. [PubMed] [Google Scholar]
- Nunn MF, Seeburg PH, Moscovici C, Duesberg PH. Tripartite structure of the avian erythroblastosis virus E26 transforming gene. Nature. 1983 Nov 24;306(5941):391–395. [PubMed] [Google Scholar]
- Moscovici MG, Jurdic P, Samarut J, Gazzolo L, Mura CV, Moscovici C. Characterization of the hemopoietic target cells for the avian leukemia virus E26. Virology. 1983 Aug;129(1):65–78. [PubMed] [Google Scholar]
- Duprey SP, Boettiger D. Developmental regulation of c-myb in normal myeloid progenitor cells. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6937–6941. [PMC free article] [PubMed] [Google Scholar]
- Sheiness D, Gardinier M. Expression of a proto-oncogene (proto-myb) in hemopoietic tissues of mice. Mol Cell Biol. 1984 Jul;4(7):1206–1212. [PMC free article] [PubMed] [Google Scholar]
- Dudek H, Reddy EP. Identification of two translational products for c-myb. Oncogene. 1989 Sep;4(9):1061–1066. [PubMed] [Google Scholar]
- Shen-Ong GL, Lüscher B, Eisenman RN. A second c-myb protein is translated from an alternatively spliced mRNA expressed from normal and 5'-disrupted myb loci. Mol Cell Biol. 1989 Dec;9(12):5456–5463. [PMC free article] [PubMed] [Google Scholar]
- Rosson D, Reddy EP. Nucleotide sequence of chicken c-myb complementary DNA and implications for myb oncogene activation. Nature. 1986 Feb 13;319(6054):604–606. [PubMed] [Google Scholar]
- Shen-Ong GL, Morse HC, 3rd, Potter M, Mushinski JF. Two modes of c-myb activation in virus-induced mouse myeloid tumors. Mol Cell Biol. 1986 Feb;6(2):380–392. [PMC free article] [PubMed] [Google Scholar]
- Weinstein Y, Ihle JN, Lavu S, Reddy EP. Truncation of the c-myb gene by a retroviral integration in an interleukin 3-dependent myeloid leukemia cell line. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5010–5014. [PMC free article] [PubMed] [Google Scholar]
- Boyle WJ, Lipsick JS, Baluda MA. Antibodies to the evolutionarily conserved amino-terminal region of the v-myb-encoded protein detect the c-myb protein in widely divergent metazoan species. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4685–4689. [PMC free article] [PubMed] [Google Scholar]
- Biedenkapp H, Borgmeyer U, Sippel AE, Klempnauer KH. Viral myb oncogene encodes a sequence-specific DNA-binding activity. Nature. 1988 Oct 27;335(6193):835–837. [PubMed] [Google Scholar]
- Weston K, Bishop JM. Transcriptional activation by the v-myb oncogene and its cellular progenitor, c-myb. Cell. 1989 Jul 14;58(1):85–93. [PubMed] [Google Scholar]
- Sakura H, Kanei-Ishii C, Nagase T, Nakagoshi H, Gonda TJ, Ishii S. Delineation of three functional domains of the transcriptional activator encoded by the c-myb protooncogene. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5758–5762. [PMC free article] [PubMed] [Google Scholar]
- Kalkbrenner F, Guehmann S, Moelling K. Transcriptional activation by human c-myb and v-myb genes. Oncogene. 1990 May;5(5):657–661. [PubMed] [Google Scholar]
- Ibanez CE, Lipsick JS. trans activation of gene expression by v-myb. Mol Cell Biol. 1990 May;10(5):2285–2293. [PMC free article] [PubMed] [Google Scholar]
- Ness SA, 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. [PubMed] [Google Scholar]
- Cullen BR. Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell. 1986 Sep 26;46(7):973–982. [PubMed] [Google Scholar]
- Rosson D, Dugan D, Reddy EP. Aberrant splicing events that are induced by proviral integration: implications for myb oncogene activation. Proc Natl Acad Sci U S A. 1987 May;84(10):3171–3175. [PMC free article] [PubMed] [Google Scholar]
- Saikumar P, Murali R, Reddy EP. Role of tryptophan repeats and flanking amino acids in Myb-DNA interactions. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8452–8456. [PMC free article] [PubMed] [Google Scholar]
- Nordeen SK. Luciferase reporter gene vectors for analysis of promoters and enhancers. Biotechniques. 1988 May;6(5):454–458. [PubMed] [Google Scholar]
- Curran T, Gordon MB, Rubino KL, Sambucetti LC. Isolation and characterization of the c-fos(rat) cDNA and analysis of post-translational modification in vitro. Oncogene. 1987;2(1):79–84. [PubMed] [Google Scholar]
- Southern PJ, Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
- Rauscher FJ, 3rd, Voulalas PJ, Franza BR, Jr, Curran T. Fos and Jun bind cooperatively to the AP-1 site: reconstitution in vitro. Genes Dev. 1988 Dec;2(12B):1687–1699. [PubMed] [Google Scholar]
- Green S, Issemann I, Sheer E. A versatile in vivo and in vitro eukaryotic expression vector for protein engineering. Nucleic Acids Res. 1988 Jan 11;16(1):369–369. [PMC free article] [PubMed] [Google Scholar]
- Miyamoto C, Chizzonite R, Crowl R, Rupprecht K, Kramer R, Schaber M, Kumar G, Poonian M, Ju G. Molecular cloning and regulated expression of the human c-myc gene in Escherichia coli and Saccharomyces cerevisiae: comparison of the protein products. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7232–7236. [PMC free article] [PubMed] [Google Scholar]
- Reddy ES, Rao VN. Structure, expression and alternative splicing of the human c-ets-1 proto-oncogene. Oncogene Res. 1988;3(3):239–246. [PubMed] [Google Scholar]
- Abate C, Luk D, Gentz R, Rauscher FJ, 3rd, Curran T. Expression and purification of the leucine zipper and DNA-binding domains of Fos and Jun: both Fos and Jun contact DNA directly. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1032–1036. [PMC free article] [PubMed] [Google Scholar]
- Moscovici C, Moscovici MG, Jimenez H, Lai MM, Hayman MJ, Vogt PK. Continuous tissue culture cell lines derived from chemically induced tumors of Japanese quail. Cell. 1977 May;11(1):95–103. [PubMed] [Google Scholar]
- de Wet JR, Wood KV, DeLuca M, Helinski DR, Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. [PMC free article] [PubMed] [Google Scholar]
- Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. [PubMed] [Google Scholar]
- Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed] [Google Scholar]
- Dasgupta P, Saikumar P, Reddy CD, Reddy EP. Myb protein binds to human immunodeficiency virus 1 long terminal repeat (LTR) sequences and transactivates LTR-mediated transcription. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8090–8094. [PMC free article] [PubMed] [Google Scholar]
- Dudek H, Reddy EP. Murine myeloid leukemias with aberrant myb loci show heterogeneous expression of novel myb proteins. Oncogene. 1989 Dec;4(12):1489–1495. [PubMed] [Google Scholar]
- Wasylyk B, Wasylyk C, Flores P, Begue A, Leprince D, Stehelin D. The c-ets proto-oncogenes encode transcription factors that cooperate with c-Fos and c-Jun for transcriptional activation. Nature. 1990 Jul 12;346(6280):191–193. [PubMed] [Google Scholar]
- Gunther CV, Nye JA, Bryner RS, Graves BJ. Sequence-specific DNA binding of the proto-oncoprotein ets-1 defines a transcriptional activator sequence within the long terminal repeat of the Moloney murine sarcoma virus. Genes Dev. 1990 Apr;4(4):667–679. [PubMed] [Google Scholar]
- Ho IC, Bhat NK, Gottschalk LR, Lindsten T, Thompson CB, Papas TS, Leiden JM. Sequence-specific binding of human Ets-1 to the T cell receptor alpha gene enhancer. Science. 1990 Nov 9;250(4982):814–818. [PubMed] [Google Scholar]
- Klemsz MJ, McKercher SR, Celada A, Van Beveren C, Maki RA. The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene. Cell. 1990 Apr 6;61(1):113–124. [PubMed] [Google Scholar]
- Bosselut R, Duvall JF, Gégonne A, Bailly M, Hémar A, Brady J, Ghysdael J. The product of the c-ets-1 proto-oncogene and the related Ets2 protein act as transcriptional activators of the long terminal repeat of human T cell leukemia virus HTLV-1. EMBO J. 1990 Oct;9(10):3137–3144. [PMC free article] [PubMed] [Google Scholar]
- Chen JH. The proto-oncogene c-ets is preferentially expressed in lymphoid cells. Mol Cell Biol. 1985 Nov;5(11):2993–3000. [PMC free article] [PubMed] [Google Scholar]
- Bhat NK, Thompson CB, Lindsten T, June CH, Fujiwara S, Koizumi S, Fisher RJ, Papas TS. Reciprocal expression of human ETS1 and ETS2 genes during T-cell activation: regulatory role for the protooncogene ETS1. Proc Natl Acad Sci U S A. 1990 May;87(10):3723–3727. [PMC free article] [PubMed] [Google Scholar]
- Metz T, Graf T. Fusion of the nuclear oncoproteins v-Myb and v-Ets is required for the leukemogenicity of E26 virus. Cell. 1991 Jul 12;66(1):95–105. [PubMed] [Google Scholar]
- Johnson PF, McKnight SL. Eukaryotic transcriptional regulatory proteins. Annu Rev Biochem. 1989;58:799–839. [PubMed] [Google Scholar]
- Frankel AD, Kim PS. Modular structure of transcription factors: implications for gene regulation. Cell. 1991 May 31;65(5):717–719. [PubMed] [Google Scholar]
- 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. [PubMed] [Google Scholar]



