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

Abstract

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 H transmembrane molecule belonging to the tumor necrosis factor family and is constitutively expressed on HTLV-I-producing cells but not normal resting T cells. The transcriptional 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-κB-like elements (1 and 2) were present in the regulatory region. Both NF-κB-like elements were able to bind to NF-κB or its related factor(s) in a Tax-dependent manner. Chloramphenicol acetyltransferase assays indicated that NF-κB-like element 1 was Tax-responsive, although the activity was lower than that the native promoter. NF-κB-like element 2 elevated promoter activity when combined with NF-κB-like element 1, indicating cooperative function of the elements for maximum promoter function. Unlike typical NF-κB elements, the NF-κB-like elements in gp34 were not activated by treatment of Jurkat cells with phorbol ester despite induction of the NF-κB-like binding activity. Chloramphenicol acetyltransferase reporter assays using the region upstream of the NF-κB- like elements identified an upstream region that reduced transcription from cognate and noncognate core promoters in a Tax-independent manner. Our results imply complex regulation of expression of the gp34 gene and suggest implication of gp34 in proliferation of HTLV-I infected T cells.