Activation of oncogenic transcription factor AP-1 in T cells infected with human T cell leukemia virus type 1.
Human T cell leukemia virus type 1 (HTLV-1) Tax protein transforms primary human T cells in vitro. We previously showed that Tax induces the expression of various family members of the transcription factor AP-1 such as c-Jun, JunD, c-Fos, and Fra-1 at the mRNA level in T cells. In this study, we have examined the ability of Tax to activate transcription through the AP-1-binding site (AP-1 site). A transient transfection study showed that Tax can activate transcription through the AP-1-binding site in a human T cell line, whereas any combination of AP-1 proteins did so much less than Tax, indicating that the activation of the AP-1 site by Tax may require a mechanism other than the induction of AP-1 mRNA. Fresh peripheral blood leukemia cells of all surveyed ATL patients displayed constitutive AP-1 DNA-binding activity, whereas no normal individuals did. However, the HTLV-1 genes, including tax, are not significantly expressed in fresh leukemia cells from ATL patients. Our present results suggest that activation of AP-1 occurs through Tax-dependent and -independent mechanisms in HTLV-1-infected T cells, which may play some roles in dysregulated phenotypes of HTLV-1-infected cells.
Fujii
M
M
Department of Virology, Niigata University School of Medicine, Asahimachi-Dori, Niigata 951-8510, Japan.
Iwai
K
K
Oie
M
M
Fukushi
M
M
Yamamoto
N
N
Kannagi
M
M
Mori
N
N
D000818:Animals; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D016356:Gene Products, tax / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism / Q000821:virology*; D051379:Mice; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation
D016356:Gene Products, tax; D018808:Transcription Factor AP-1