Evi-1 raises AP-1 activity and stimulates c-fos promoter transactivation with dependence on the second zinc finger domain.
Evi-1 is a gene, encoding a zinc finger protein, associated with a common viral integration site in murine leukemias. It is suggested that Evi-1 plays important roles in embryogenesis and transformation of myeloid cells. To elucidate mechanisms by which Evi-1 induces such biological effects, we analyzed the relationship between Evi-1 and AP-1 which could regulate cellular proliferation and differentiation. When Evi-1 was expressed, transactivation through a 12-O-tetradecanoylphorbol 13-acetate-responsive element was observed in NIH3T3 and P19 cells. Evi-1-transfected P19 cells showed some differentiated phenotypes and increased expression of endogenous c-Jun and c-Fos. These results indicate that Evi-1 raises AP-1 activity. Evi-1 caused stimulation of the c-fos promoter transactivation, which seems to be a main mechanism of AP-1 activation, through at least two portions of the promoter. Evi-1 has the first zinc finger domain at the N terminus and the second zinc finger domain near the C-terminus. We constructed deletion mutants of Evi-1 and investigated the functions of these domains. It was shown that the second zinc finger domain is essential for the activation of AP-1 and transactivation of the c-fos promoter.
Tanaka
T
T
Department of Molecular Biology, Jichi Medical School, Tochigi, Japan.
Nishida
J
J
Mitani
K
K
Ogawa
S
S
Yazaki
Y
Y
Hirai
H
H
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016762:Genes, fos; D016758:Genes, jun; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D011519:Proto-Oncogenes; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C499305:Mecom protein, mouse; D009838:Oligodeoxyribonucleotides; D018808:Transcription Factor AP-1; D014157:Transcription Factors