Tax proteins of human T-cell leukemia virus type 1 and 2 induce expression of the gene encoding erythroid-potentiating activity (tissue inhibitor of metalloproteinases-1, TIMP-1).
A growth factor-like activity for erythroid cells (erythroid-potentiating activity) is produced by the T-cells infected with human T-cell leukemia virus type 2 (HTLV-2) (Gasson, J. C., Golde, D. W., Kaufman, S. E., Westbrook, C. A., Hewick, R. M., Kaufmann, R. J., Wong, G. G., Temple, P. A., Leary, A. C., Brown, E. L., Orr, E. C., and Clark, S. C. (1985) Nature 315, 768-771) and is reportedly identical with tissue inhibitors of matrix metalloproteinases-1 (TIMP-1) (Docherty, A. J. P., Lyons, A., Smith, B. J., Wright, E. M., Stephens, P. E., Harris, T. J. R., Murphy, G., and Reynolds, J. J. (1985) Nature 318, 66-69). We found that adult T-cell leukemia cell lines infected with HTLV-1 also express high levels of a TIMP-1 transcript. A viral transactivator of HTLV-1, Tax1, in a human T-cell line (Jurkat), was sufficient to stimulate transcription of the TIMP-1 gene. Deletion and mutation analysis of the TIMP-1 gene promoter showed that the AP-1 binding site in the 38-base pair sequence conserved between the human and mouse genes was essential for activation by Tax1. The transactivator of HTLV-2 also stimulated the promoter through the same cis-element. The reported growth-promoting activity of TIMP-1 against erythroid cells and potentially against HTLV-1-infected T-cells may modulate the clinical course of adult T-cell leukemia.
Uchijima
M
M
Department of Molecular Virology and Oncology, Kanazawa University, Ishikawa, Japan.
Sato
H
H
Fujii
M
M
Seiki
M
M
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000502:physiology*; D006023:Glycoproteins / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D015367:Human T-lymphotropic virus 2 / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000382:microbiology; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases; D014157:Transcription Factors; D015533:Transcriptional Activation
D016356:Gene Products, tax; D006023:Glycoproteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D014157:Transcription Factors