Human T-cell leukemia virus type I Tax transactivates human interleukin 8 gene through acting concurrently on AP-1 and nuclear factor-kappaB-like sites.
The transactivator protein, Tax, from the human T-cell leukemia virus type I (HTLV-I) transactivates both viral and cellular genes. Previously, we had shown that interleukin 8 (IL-8) is constitutively expressed in HTLV-I-infected cells and in cells transiently expressing Tax. We show here that the IL-8 promoter is Tax responsive in Jurkat T cells. Furthermore, using several deletion and mutated plasmids of the 5'-flanking regulatory region of the IL-8 gene linked to the luciferase gene as a reporter and mutant tax gene expression vectors, we have established that both AP-1 at -126 to -120 and nuclear factor (NF)-kappaB-like cis-element at -80 to -71 are essential and sufficient for the induction of the IL-8 gene by HTLV-I Tax. In addition, overexpression of the dominant-negative mutants of NF-kappaB inhibitor molecules, IkappaBalpha and IkappaBbeta, abolished the Tax-induced activation of IL-8 gene. Gel mobility shift assays detected proteins specifically binding to the AP-1 and NF-kappaB-like sites in Tax-expressing T-cell lines infected with HTLV-I. Similarly, the nuclear translocation of proteins specifically bound to these two motifs was shown in JPX-9 cells, a subclone of Jurkat cells, carrying the Tax sequences under the control of an inducible promoter. Taken together, these results suggest that the cooperation of transcription factors NF-kappaB and AP-1 is essential for transactivation of IL-8 gene by HTLV-I Tax.
Mori
N
N
Department of Preventive Medicine and AIDS Research, Research Field of Pathogenesis and Clinical Sciences, Institute of Tropical Medicine, Nagasaki University, Sakamoto, Japan.
Mukaida
N
N
Ballard
D W
DW
Matsushima
K
K
Yamamoto
N
N
D001665:Binding Sites; D002460:Cell Line; D016356:Gene Products, tax / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D051841:Transcription Factor RelB; D014157:Transcription Factors; D015533:Transcriptional Activation
D016356:Gene Products, tax; D016209:Interleukin-8; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051841:Transcription Factor RelB