Transrepression of lck gene expression by human T-cell leukemia virus type 1-encoded p40tax.
To understand the mechanism of p56lck protein downregulation observed in human T cells infected by human T-cell leukemia virus type 1 (HTLV-1), we have investigated the ability of the 3' end of the HTLV-1 genome as well as that of the tax and rex genes to modulate p56lck protein expression and p56lck mRNA synthesis. By using Jurkat T cells stably transfected with constructs that expressed either the 3' end of the HTLV-1 genome (JK C11-pMTEX), the tax gene (JK52-Tax) or the rex gene (JK9-Rex), we found that the expression of p40tax (Tax) was sufficient to modulate p56lck protein expression. Similarly, we found that the expression of the mRNA which encoded p56lck was repressed in Jurkat T cells which expressed Tax. This downregulation was shown to be proportional to the amount of tax mRNA found in the transfected cells, as evidenced by experiments that used cells (JPX-9) stably transfected with a tax gene driven by a cadmium-inducible promoter. Furthermore, cadmium induction of Tax in JPX-9 cells transiently transfected with a construct containing the chloramphenicol acetyltransferase (CAT) gene under control of the lck distal promoter (lck DP-CAT) resulted in the downregulation of CAT gene expression. In contrast, cadmium induction of Tax in JPX-9 cells transiently transfected with a CAT construct driven by a lck DP with a deletion extending from position -259 to -253 (a sequence corresponding to a putative E-Box) did not modulate CAT gene expression, suggesting that the effect of Tax on p56lck is mediated through an E-Box binding protein.
Lemasson
I
I
Laboratoire d'Immunologie des Infections Rétrovirales, CNRS ERS 155-INSERM U249, Institut de Biologie, Montpellier, France.
Robert-Hebmann
V
V
Hamaia
S
S
Duc Dodon
M
M
Gazzolo
L
L
Devaux
C
C
D002460:Cell Line; D002461:Cell Line, Transformed; D015967:Gene Expression Regulation, Viral; D016370:Gene Products, rex / Q000235:genetics*; D016356:Gene Products, tax / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D009856:Oncogene Proteins, Viral / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D012097:Repressor Proteins / Q000235:genetics*; D019061:src-Family Kinases / Q000235:genetics*
D016370:Gene Products, rex; D016356:Gene Products, tax; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012097:Repressor Proteins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases