C-JUN INHIBITS NF-E2 TRANSCRIPTIONAL ACTIVITY IN ASSOCIATION WITH P18MAF IN FRIEND-ERYTHROLEUKEMIA CELLS/

We have reported previously that antisense c-jun overcomes a block of Friend erythroleukemia cells to differentiation suggesting that the fa ctor c-Jun may be an important negative regulator of erythroid differe ntiation, The recently described erythroid transcription factor NF-E2 plays an important role in the regulation of the transcription of glob in 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 transcrip tional activation from them, we have compared the activity of AP-1 and NF-E2 in transient transcriptional assays, in erythroid and nonerythr oid cells in the presence of c-jan sense and antisense expression vect ors. In non-erythroid cells, c-Jun activates and NF-E2p18 inhibits bot h 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 posi tive regulator of NF-E2 activity in erythroid cells. c-Jun alone is al so a positive regulator of NF-E2 activity in erythroid cells but in as sociation with NF-E2p18 inhibits this activity, Moreover antisense c-j un increases endogenous NF-E2 activity in erythroid cells. These resul ts suggest that c-Jun could act as a repressor of NF-E2 transcriptiona l activity by forming inactive c-Jun/NF-E2p18 heterocomplexes which in terfer with the transcription of globin genes in Friend erythroleukemi a cells.