EVI-1 RAISES AP-1 ACTIVITY AND STIMULATES C-FOS PROMOTER TRANSACTIVATION WITH DEPENDENCE ON THE 2ND ZINC-FINGER DOMAIN

Evi-1 is a gene, encoding a zinc finger protein, associated with a com mon viral integration site in murine leukemias. It is suggested that E vi-1 plays important roles in embryogenesis and transformation of myel oid cells. To elucidate mechanisms by which Evi-1 induces such biologi cal 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 incr eased 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-fo s 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 fin ger 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,