Cell-type-specific transactivation of the parathyroid hormone-related protein gene promoter by the human T-cell leukemia virus type I (HTLV-I) tax and HTLV-II tax proteins.
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.
Ejima
E
E
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048.
Rosenblatt
J D
JD
Massari
M
M
Quan
E
E
Stephens
D
D
Rosen
C A
CA
Prager
D
D
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017353:Gene Deletion; D016356:Gene Products, tax / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015368:Human T-lymphotropic virus 1; D015367:Human T-lymphotropic virus 2; D006801:Humans; D006922:Hylobates; D008969:Molecular Sequence Data; D016296:Mutagenesis; D044162:Parathyroid Hormone-Related Protein; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
D016356:Gene Products, tax; C000715470:MAS1 protein, human; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun