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. 1995 Apr;15(4):2180–2190. doi: 10.1128/mcb.15.4.2180

Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF-E2 transcription factor.

K Kataoka 1, K Igarashi 1, K Itoh 1, K T Fujiwara 1, M Noda 1, M Yamamoto 1, M Nishizawa 1
PMCID: PMC230446  PMID: 7891713

Abstract

The maf oncogene encodes a bZip nuclear protein which recognizes sequences related to an AP-1 site either as a homodimer or as heterodimers with Fos and Jun. We describe here a novel maf-related gene, mafG, which shows extensive homology with two other maf-related genes, mafK and mafF. These three maf-related genes encode small basic-leucine zipper proteins lacking the trans-activator domain of v-Maf. Bacterially expressed small Maf proteins bind to DNA as homodimers with a sequence recognition profile that is virtually identical to that of v-Maf. As we have previously described, the three small Maf proteins also dimerize with the large subunit of NF-E2 (p45) to form an erythroid cell-specific transcription factor, NF-E2, which has distinct DNA-binding specificity. This study shows that the small Maf proteins can also dimerize among themselves and with Fos and a newly identified p45-related molecule (Ech) but not with v-Maf or Jun. Although the small Maf proteins preferentially recognize the consensus NF-E2 sequence as heterodimers with either NF-E2 p45, Ech, or Fos, these heterodimers seemed to be different in their transactivation potentials. Coexpression of Fos and small Mafs could not activate a promoter with tandem repeats of the NF-E2 site. These results raise the possibility that tissue-specific gene expression and differentiation of erythroid cells are regulated by competition among Fos, NF-E2 p45, and Ech for small Maf proteins and for binding sites.

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Selected References

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  1. Abate C., Luk D., Curran T. Transcriptional regulation by Fos and Jun in vitro: interaction among multiple activator and regulatory domains. Mol Cell Biol. 1991 Jul;11(7):3624–3632. doi: 10.1128/mcb.11.7.3624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andrews N. C., Erdjument-Bromage H., Davidson M. B., Tempst P., Orkin S. H. Erythroid transcription factor NF-E2 is a haematopoietic-specific basic-leucine zipper protein. Nature. 1993 Apr 22;362(6422):722–728. doi: 10.1038/362722a0. [DOI] [PubMed] [Google Scholar]
  3. Andrews N. C., Kotkow K. J., Ney P. A., Erdjument-Bromage H., Tempst P., Orkin S. H. The ubiquitous subunit of erythroid transcription factor NF-E2 is a small basic-leucine zipper protein related to the v-maf oncogene. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11488–11492. doi: 10.1073/pnas.90.24.11488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Auwerx J., Staels B., Sassone-Corsi P. Coupled and uncoupled induction of fos and jun transcription by different second messengers in cells of hematopoietic origin. Nucleic Acids Res. 1990 Jan 25;18(2):221–228. doi: 10.1093/nar/18.2.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Castellazzi M., Spyrou G., La Vista N., Dangy J. P., Piu F., Yaniv M., Brun G. Overexpression of c-jun, junB, or junD affects cell growth differently. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8890–8894. doi: 10.1073/pnas.88.20.8890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Caterina J. J., Donze D., Sun C. W., Ciavatta D. J., Townes T. M. Cloning and functional characterization of LCR-F1: a bZIP transcription factor that activates erythroid-specific, human globin gene expression. Nucleic Acids Res. 1994 Jun 25;22(12):2383–2391. doi: 10.1093/nar/22.12.2383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chan J. Y., Han X. L., Kan Y. W. Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11371–11375. doi: 10.1073/pnas.90.23.11371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chan J. Y., Han X. L., Kan Y. W. Isolation of cDNA encoding the human NF-E2 protein. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11366–11370. doi: 10.1073/pnas.90.23.11366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chiu R., Angel P., Karin M. Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun. Cell. 1989 Dec 22;59(6):979–986. doi: 10.1016/0092-8674(89)90754-x. [DOI] [PubMed] [Google Scholar]
  10. Conscience J. F., Verrier B., Martin G. Interleukin-3-dependent expression of the c-myc and c-fos proto-oncogenes in hemopoietic cell lines. EMBO J. 1986 Feb;5(2):317–323. doi: 10.1002/j.1460-2075.1986.tb04215.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Damm K., Thompson C. C., Evans R. M. Protein encoded by v-erbA functions as a thyroid-hormone receptor antagonist. Nature. 1989 Jun 22;339(6226):593–597. doi: 10.1038/339593a0. [DOI] [PubMed] [Google Scholar]
  12. Distel R. J., Spiegelman B. M. Protooncogene c-fos as a transcription factor. Adv Cancer Res. 1990;55:37–55. doi: 10.1016/s0065-230x(08)60467-4. [DOI] [PubMed] [Google Scholar]
  13. Fujiwara K. T., Ashida K., Nishina H., Iba H., Miyajima N., Nishizawa M., Kawai S. The chicken c-fos gene: cloning and nucleotide sequence analysis. J Virol. 1987 Dec;61(12):4012–4018. doi: 10.1128/jvi.61.12.4012-4018.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fujiwara K. T., Kataoka K., Nishizawa M. Two new members of the maf oncogene family, mafK and mafF, encode nuclear b-Zip proteins lacking putative trans-activator domain. Oncogene. 1993 Sep;8(9):2371–2380. [PubMed] [Google Scholar]
  15. Garcia M., Samarut J. v-jun cooperates with v-erbB to transform the thrombocytic/megakaryocytic lineage. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8837–8841. doi: 10.1073/pnas.90.19.8837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gardiner-Garden M., Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987 Jul 20;196(2):261–282. doi: 10.1016/0022-2836(87)90689-9. [DOI] [PubMed] [Google Scholar]
  17. Hartl M., Vogt P. K. Oncogenic transformation by Jun: role of transactivation and homodimerization. Cell Growth Differ. 1992 Dec;3(12):899–908. [PubMed] [Google Scholar]
  18. Hirai S. I., Ryseck R. P., Mechta F., Bravo R., Yaniv M. Characterization of junD: a new member of the jun proto-oncogene family. EMBO J. 1989 May;8(5):1433–1439. doi: 10.1002/j.1460-2075.1989.tb03525.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Igarashi K., Kataoka K., Itoh K., Hayashi N., Nishizawa M., Yamamoto M. Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins. Nature. 1994 Feb 10;367(6463):568–572. doi: 10.1038/367568a0. [DOI] [PubMed] [Google Scholar]
  20. Kataoka K., Fujiwara K. T., Noda M., Nishizawa M. MafB, a new Maf family transcription activator that can associate with Maf and Fos but not with Jun. Mol Cell Biol. 1994 Nov;14(11):7581–7591. doi: 10.1128/mcb.14.11.7581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kataoka K., Nishizawa M., Kawai S. Structure-function analysis of the maf oncogene product, a member of the b-Zip protein family. J Virol. 1993 Apr;67(4):2133–2141. doi: 10.1128/jvi.67.4.2133-2141.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kataoka K., Noda M., Nishizawa M. Maf nuclear oncoprotein recognizes sequences related to an AP-1 site and forms heterodimers with both Fos and Jun. Mol Cell Biol. 1994 Jan;14(1):700–712. doi: 10.1128/mcb.14.1.700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kawai S., Goto N., Kataoka K., Saegusa T., Shinno-Kohno H., Nishizawa M. Isolation of the avian transforming retrovirus, AS42, carrying the v-maf oncogene and initial characterization of its gene product. Virology. 1992 Jun;188(2):778–784. doi: 10.1016/0042-6822(92)90532-t. [DOI] [PubMed] [Google Scholar]
  24. Kerppola T. K., Curran T. A conserved region adjacent to the basic domain is required for recognition of an extended DNA binding site by Maf/Nrl family proteins. Oncogene. 1994 Nov;9(11):3149–3158. [PubMed] [Google Scholar]
  25. Kerppola T. K., Curran T. Maf and Nrl can bind to AP-1 sites and form heterodimers with Fos and Jun. Oncogene. 1994 Mar;9(3):675–684. [PubMed] [Google Scholar]
  26. Kunkel T. A., Roberts J. D., Zakour R. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Methods Enzymol. 1987;154:367–382. doi: 10.1016/0076-6879(87)54085-x. [DOI] [PubMed] [Google Scholar]
  27. Luna L., Johnsen O., Skartlien A. H., Pedeutour F., Turc-Carel C., Prydz H., Kolstø A. B. Molecular cloning of a putative novel human bZIP transcription factor on chromosome 17q22. Genomics. 1994 Aug;22(3):553–562. doi: 10.1006/geno.1994.1428. [DOI] [PubMed] [Google Scholar]
  28. Mignotte V., Eleouet J. F., Raich N., Romeo P. H. Cis- and trans-acting elements involved in the regulation of the erythroid promoter of the human porphobilinogen deaminase gene. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6548–6552. doi: 10.1073/pnas.86.17.6548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mignotte V., Navarro S., Eleouet J. F., Zon L. I., Romeo P. H. The extinction of erythroid genes after tetradecanoylphorbol acetate treatment of erythroleukemic cells correlates with down-regulation of the tissue-specific factors NF-E1 and NF-E2. J Biol Chem. 1990 Dec 25;265(36):22090–22092. [PubMed] [Google Scholar]
  30. Mignotte V., Wall L., deBoer E., Grosveld F., Romeo P. H. Two tissue-specific factors bind the erythroid promoter of the human porphobilinogen deaminase gene. Nucleic Acids Res. 1989 Jan 11;17(1):37–54. doi: 10.1093/nar/17.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mizushima S., Nagata S. pEF-BOS, a powerful mammalian expression vector. Nucleic Acids Res. 1990 Sep 11;18(17):5322–5322. doi: 10.1093/nar/18.17.5322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Moi P., Chan K., Asunis I., Cao A., Kan Y. W. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9926–9930. doi: 10.1073/pnas.91.21.9926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Müller R., Curran T., Müller D., Guilbert L. Induction of c-fos during myelomonocytic differentiation and macrophage proliferation. Nature. 1985 Apr 11;314(6011):546–548. doi: 10.1038/314546a0. [DOI] [PubMed] [Google Scholar]
  35. Ney P. A., Andrews N. C., Jane S. M., Safer B., Purucker M. E., Weremowicz S., Morton C. C., Goff S. C., Orkin S. H., Nienhuis A. W. Purification of the human NF-E2 complex: cDNA cloning of the hematopoietic cell-specific subunit and evidence for an associated partner. Mol Cell Biol. 1993 Sep;13(9):5604–5612. doi: 10.1128/mcb.13.9.5604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Nishizawa M., Goto N., Kawai S. An avian transforming retrovirus isolated from a nephroblastoma that carries the fos gene as the oncogene. J Virol. 1987 Dec;61(12):3733–3740. doi: 10.1128/jvi.61.12.3733-3740.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Nishizawa M., Kataoka K., Goto N., Fujiwara K. T., Kawai S. v-maf, a viral oncogene that encodes a "leucine zipper" motif. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7711–7715. doi: 10.1073/pnas.86.20.7711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Papayannopoulou T., Nakamoto B., Yokochi T., Chait A., Kannagi R. Human erythroleukemia cell line (HEL) undergoes a drastic macrophage-like shift with TPA. Blood. 1983 Oct;62(4):832–845. [PubMed] [Google Scholar]
  39. Pfarr C. M., Mechta F., Spyrou G., Lallemand D., Carillo S., Yaniv M. Mouse JunD negatively regulates fibroblast growth and antagonizes transformation by ras. Cell. 1994 Feb 25;76(4):747–760. doi: 10.1016/0092-8674(94)90513-4. [DOI] [PubMed] [Google Scholar]
  40. Prochownik E. V., Smith M. J., Snyder K., Emeagwali D. Amplified expression of three jun family members inhibits erythroleukemia differentiation. Blood. 1990 Nov 1;76(9):1830–1837. [PubMed] [Google Scholar]
  41. Ryder K., Lanahan A., Perez-Albuerne E., Nathans D. jun-D: a third member of the jun gene family. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1500–1503. doi: 10.1073/pnas.86.5.1500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Ryder K., Lau L. F., Nathans D. A gene activated by growth factors is related to the oncogene v-jun. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1487–1491. doi: 10.1073/pnas.85.5.1487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Sap J., Muñoz A., Damm K., Goldberg Y., Ghysdael J., Leutz A., Beug H., Vennström B. The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature. 1986 Dec 18;324(6098):635–640. doi: 10.1038/324635a0. [DOI] [PubMed] [Google Scholar]
  44. Sap J., Muñoz A., Schmitt J., Stunnenberg H., Vennström B. Repression of transcription mediated at a thyroid hormone response element by the v-erb-A oncogene product. Nature. 1989 Jul 20;340(6230):242–244. doi: 10.1038/340242a0. [DOI] [PubMed] [Google Scholar]
  45. Schütte J., Viallet J., Nau M., Segal S., Fedorko J., Minna J. jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun. Cell. 1989 Dec 22;59(6):987–997. doi: 10.1016/0092-8674(89)90755-1. [DOI] [PubMed] [Google Scholar]
  46. Sharif M., Privalsky M. L. v-erbA oncogene function in neoplasia correlates with its ability to repress retinoic acid receptor action. Cell. 1991 Sep 6;66(5):885–893. doi: 10.1016/0092-8674(91)90435-2. [DOI] [PubMed] [Google Scholar]
  47. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  48. Solomon W. B., Lin C. H., Palma J., Gao X. Y., Wu S. Suppression of a cellular differentiation program by phorbol esters coincides with inhibition of binding of a cell-specific transcription factor (NF-E2) to an enhancer element required for expression of an erythroid-specific gene. J Biol Chem. 1993 Mar 5;268(7):5089–5096. [PubMed] [Google Scholar]
  49. Sukegawa J., Semba K., Yamanashi Y., Nishizawa M., Miyajima N., Yamamoto T., Toyoshima K. Characterization of cDNA clones for the human c-yes gene. Mol Cell Biol. 1987 Jan;7(1):41–47. doi: 10.1128/mcb.7.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Swaroop A., Xu J. Z., Pawar H., Jackson A., Skolnick C., Agarwal N. A conserved retina-specific gene encodes a basic motif/leucine zipper domain. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):266–270. doi: 10.1073/pnas.89.1.266. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Todokoro K., Watson R. J., Higo H., Amanuma H., Kuramochi S., Yanagisawa H., Ikawa Y. Down-regulation of c-myb gene expression is a prerequisite for erythropoietin-induced erythroid differentiation. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8900–8904. doi: 10.1073/pnas.85.23.8900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Vogt P. K., Bos T. J. jun: oncogene and transcription factor. Adv Cancer Res. 1990;55:1–35. doi: 10.1016/s0065-230x(08)60466-2. [DOI] [PubMed] [Google Scholar]
  53. Yamamoto M., Ko L. J., Leonard M. W., Beug H., Orkin S. H., Engel J. D. Activity and tissue-specific expression of the transcription factor NF-E1 multigene family. Genes Dev. 1990 Oct;4(10):1650–1662. doi: 10.1101/gad.4.10.1650. [DOI] [PubMed] [Google Scholar]

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