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)

• Published in: The Journal of biological chemistry Vol. 269; no. 21; pp. 14946 - 14950
• Main Authors: UCHIJIMA, M, SATO, H, FUJII, M, SEIKI, M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 27-05-1994
• Subjects: AIDS/HIV; Analytical, structural and metabolic biochemistry; Animals; Base Sequence; Binding Sites; Biological and medical sciences; Cells, Cultured; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Viral; Gene Products, tax - physiology; Glycoproteins - genetics; Human T-lymphotropic virus 1 - metabolism; Human T-lymphotropic virus 2 - metabolism; Humans; Hydrolases; Lymphocytes - microbiology; Mice; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Nuclear Proteins - metabolism; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-ets; Proto-Oncogene Proteins c-jun - metabolism; RNA, Messenger - metabolism; Tissue Inhibitor of Metalloproteinases; Transcription Factors; Transcription. Transcription factor. Splicing. Rna processing; Transcriptional Activation; Virus; Transcription; Erythroid cell; Enzyme; Transcription promoter; Enzyme inhibitor; Retroviridae; Hydrolases; Metalloendopeptidases; HTLV virus; Transcription factor; Proteinases
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)36557-2

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.