Abstract
The human T-cell leukemia virus type I (HTLV-I) and HTLV-II Tax proteins are potent transactivators of viral and cellular gene expression. Using deletion mutants, the downstream parathyroid hormone-related protein (PTHrP) promoter is shown to be responsive to both HTLV-I and HTLV-II Tax as well as the AP1/c-jun proto-oncogene. Transactivation of PTHrP by Tax was seen in T cells but not in B-cell lines or fibroblasts. A carboxy terminal Tax deletion mutant was deficient in transactivation of both the PTHrP and IL2R alpha promoters but not the HTLV-I long terminal repeat (LTR). Exogenous provision of NFkB rescued IL2R alpha expression but not the PTHrP promoter. Thus, HTLV-I Tax, HTLV-II Tax, and c-jun transactivate PTHrP and may contribute to the pathogenesis of hypercalcemia in adult T-cell leukemia.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Cell Line
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Gene Deletion
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Gene Products, tax / chemistry
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Gene Products, tax / genetics
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Gene Products, tax / physiology*
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Human T-lymphotropic virus 1*
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Human T-lymphotropic virus 2*
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Humans
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Hylobates
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Molecular Sequence Data
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Mutagenesis
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Parathyroid Hormone-Related Protein
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Promoter Regions, Genetic / genetics*
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Proteins / genetics*
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Proto-Oncogene Mas
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Proto-Oncogene Proteins c-jun / physiology
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Repetitive Sequences, Nucleic Acid
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Structure-Activity Relationship
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T-Lymphocytes / metabolism
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Transcriptional Activation*
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Transfection
Substances
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Gene Products, tax
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MAS1 protein, human
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PTHLH protein, human
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Parathyroid Hormone-Related Protein
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Proteins
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Proto-Oncogene Mas
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Proto-Oncogene Proteins c-jun