MOLECULAR MECHANISMS OF PROMOTER REGULATION OF THE GP34 GENE THAT IS TRANS-ACTIVATED BY AN ONCOPROTEIN TAX OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I

We investigated the molecular mechanism of transcriptional activation of the gp34 gene by the Tax oncoprotein of human T cell leukemia virus type I (HTLV-I), gp34 is a type II transmembrane molecule belonging t o the tumor necrosis factor family and is constitutively expressed on HTLV-I-producing cells but not normal resting T cells. The transcripti onal regulatory region of the gp34 gene was activated by HTLV-I Tax in the human T cell line Jurkat, in which endogenous gp34 is induced by Tax. Sequence analysis demonstrated that two NF-kappa B-like elements (1 and 2) were present in the regulatory region, Both NF-kappa B-like elements were able to bind to NF-kappa B or its related factor(s) in a Tax-dependent manner. Chloramphenicol acetyltransferase assays indica ted that NF-kappa B-like element 1 was Tax-responsive, although the ac tivity was lower than that the native promoter. NF-kappa B-like elemen t 2 elevated promoter activity when combined with NF-kappa B-like elem ent 1, indicating cooperative function of the elements for maximum pro moter function. Unlike typical NF-kappa B elements, the NF-kappa B-lik e elements in gp34 were not activated by treatment of Jurkat cells wit h phorbol ester despite induction of the NF-kappa B-like binding activ ity. Chloramphenicol acetyltransferase reporter assays using the regio n upstream of the NF-kappa B-like elements identified an upstream regi on that reduced transcription from cognate and noncognate core promote rs in a Tax-independent manner. Our results imply complex regulation o f expression of the gp34 gene and suggest implication of gp34 in proli feration of HTLV-I infected T cells.