title: c-Jun inhibits NF-E2 transcriptional activity in association with p18/maf in Friend erythroleukemia cells.
abstract: We have reported previously that antisense c-jun overcomes a block of Friend erythroleukemia cells to differentiation suggesting that the factor c-Jun may be an important negative regulator of erythroid differentiation. The recently described erythroid transcription factor NF-E2 plays an important role in the regulation of the transcription of globin genes and recognizes a sequence containing an AP-1 site. NF-E2 is a complex of two bZip proteins, p45 and p18/Maf. In order to determine whether c-Jun can interact with NF-E2/AP-1 sites to regulate transcriptional activation from them, we have compared the activity of AP-1 and NF-E2 in transient transcriptional assays, in erythroid and nonerythroid cells in the presence of c-jun sense and antisense expression vectors. In non-erythroid cells, c-Jun activates and NF-E2p18 inhibits both AP-1 and NF-E2 activities, suggesting that NF-E2/AP-1 sites function as AP-1 binding sites in these cells. In contrast, NF-E2p18 is a positive regulator of NF-E2 activity in erythroid cells. c-Jun alone is also a positive regulator of NF-E2 activity in erythroid cells but in association with NF-E2p18 inhibits this activity. Moreover antisense c-jun increases endogenous NF-E2 activity in erythroid cells. These results suggest that c-Jun could act as a repressor of NF-E2 transcriptional activity by forming inactive c-Jun/NF-E2p18 heterocomplexes which interfer with the transcription of globin genes in Friend erythroleukemia cells.
authors.affiliation: INSERM U268, Hôpital Paul Brousse, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Francastel
authors.forename: Y
authors.initials: Y
authors.lastname: Augery-Bourget
authors.forename: M
authors.initials: M
authors.lastname: Prenant
authors.forename: M
authors.initials: M
authors.lastname: Walters
authors.forename: D I
authors.initials: DI
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Robert-Lézénès
mesh_terms: D016475:3T3 Cells; D000818:Animals; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D050981:Erythroid-Specific DNA-Binding Factors; D005622:Friend murine leukemia virus; D016758:Genes, jun / Q000502:physiology*; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D050985:MafK Transcription Factor; D051379:Mice; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051257:Proto-Oncogene Proteins c-maf; D018808:Transcription Factor AP-1 / Q000502:physiology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; C495608:Maf protein, mouse; D050985:MafK Transcription Factor; C494696:Mafk protein, mouse; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; C494693:Nfe2 protein, mouse; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf; D018808:Transcription Factor AP-1; D014157:Transcription Factors