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 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-kappaB-like elements (1 and 2) were present in the regulatory region. Both NF-kappaB-like elements were able to bind to NF-kappaB or its related factor(s) in a Tax-dependent manner. Chloramphenicol acetyltransferase assays indicated that NF-kappaB-like element 1 was Tax-responsive, although the activity was lower than that the native promoter. NF-kappaB-like element 2 elevated promoter activity when combined with NF-kappaB-like element 1, indicating cooperative function of the elements for maximum promoter function. Unlike typical NF-kappaB elements, the NF-kappaB-like elements in gp34 were not activated by treatment of Jurkat cells with phorbol ester despite induction of the NF-kappaB-like binding activity. Chloramphenicol acetyltransferase reporter assays using the region upstream of the NF-kappaB-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.
Ohtani
K
K
Human Gene Sciences Center, Japan.
Tsujimoto
A
A
Tsukahara
T
T
Numata
N
N
Miura
S
S
Sugamura
K
K
Nakamura
M
M
D000954:Antigens, Surface; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D016356:Gene Products, tax / Q000502:physiology*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000737:chemistry; D009687:Nuclear Proteins / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D000954:Antigens, Surface; D004268:DNA-Binding Proteins; D016356:Gene Products, tax; D008565:Membrane Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D014409:Tumor Necrosis Factor-alpha; D015500:Chloramphenicol O-Acetyltransferase