scholarly journals trans activation of nerve growth factor in transgenic mice containing the human T-cell lymphotropic virus type I tax gene.

1991 ◽  
Vol 11 (9) ◽  
pp. 4635-4641 ◽  
Author(s):  
J E Green
Keyword(s):  
Nerve Growth Factor ◽  
T Cell ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Virus Type ◽  
Type I ◽  
Nerve Growth ◽  
Human T Cell ◽  
Responsive Element

Three lines of transgenic mice containing the human T-cell lymphotropic virus type I (HTLV-I) tax gene develop neurofibromas composed of perineural fibroblasts (S. H. Hinrichs, M. Nerenberg, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1340-1343, 1987; M. Nerenberg, S. H. Hinrichs, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1324-1327, 1987). Tumors and tumor cell lines derived from these mice produce neurite outgrowth from PC-12 cells and nerve growth factor (NGF), as determined by RNA (Northern) blot analysis and enzyme-linked immunosorbent assays. In vitro cotransfection studies demonstrate that Tax is able to trans activate the NGF promoter in NIH 3T3 fibroblast cells. The major cis-acting tax-responsive element in the NGF promoter (AGGGTGTGACGA) has 92% homology with a tax-responsive element contained within the 21-bp repeats of the HTLV-I long terminal repeat. The receptor for NGF is also expressed in the transgenic tumor cells, suggesting that Tax may activate an autocrine mechanism through the upregulation of NGF.

trans activation of nerve growth factor in transgenic mice containing the human T-cell lymphotropic virus type I tax gene

1991 ◽  
Vol 11 (9) ◽  
pp. 4635-4641
Author(s):  
J E Green
Keyword(s):  
Nerve Growth Factor ◽  
T Cell ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Virus Type ◽  
Type I ◽  
Nerve Growth ◽  
Human T Cell ◽  
Responsive Element

Three lines of transgenic mice containing the human T-cell lymphotropic virus type I (HTLV-I) tax gene develop neurofibromas composed of perineural fibroblasts (S. H. Hinrichs, M. Nerenberg, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1340-1343, 1987; M. Nerenberg, S. H. Hinrichs, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1324-1327, 1987). Tumors and tumor cell lines derived from these mice produce neurite outgrowth from PC-12 cells and nerve growth factor (NGF), as determined by RNA (Northern) blot analysis and enzyme-linked immunosorbent assays. In vitro cotransfection studies demonstrate that Tax is able to trans activate the NGF promoter in NIH 3T3 fibroblast cells. The major cis-acting tax-responsive element in the NGF promoter (AGGGTGTGACGA) has 92% homology with a tax-responsive element contained within the 21-bp repeats of the HTLV-I long terminal repeat. The receptor for NGF is also expressed in the transgenic tumor cells, suggesting that Tax may activate an autocrine mechanism through the upregulation of NGF.

scholarly journals In vitro selection of DNA elements highly responsive to the human T-cell lymphotropic virus type I transcriptional activator, Tax.

1994 ◽  
Vol 14 (1) ◽  
pp. 456-462 ◽  
Author(s):  
S Paca-Uccaralertkun ◽  
L J Zhao ◽  
N Adya ◽  
J V Cross ◽  
B R Cullen ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
In Vitro Selection ◽  
Type I ◽  
Mobility Shift ◽  
Camp Response Element ◽  
Response Element ◽  
Human T Cell ◽  
Dna Elements

The human T-cell lymphotropic virus type I (HTLV-I) transactivator, Tax, the ubiquitous transcriptional factor cyclic AMP (cAMP) response element-binding protein (CREB protein), and the 21-bp repeats in the HTLV-I transcriptional enhancer form a ternary nucleoprotein complex (L. J. Zhao and C. Z. Giam, Proc. Natl. Acad. Sci. USA 89:7070-7074, 1992). Using an antibody directed against the COOH-terminal region of Tax along with purified Tax and CREB proteins, we selected DNA elements bound specifically by the Tax-CREB complex in vitro. Two distinct but related groups of sequences containing the cAMP response element (CRE) flanked by long runs of G and C residues in the 5' and 3' regions, respectively, were preferentially recognized by Tax-CREB. In contrast, CREB alone binds only to CRE motifs (GNTGACG[T/C]) without neighboring G- or C-rich sequences. The Tax-CREB-selected sequences bear a striking resemblance to the 5' or 3' two-thirds of the HTLV-I 21-bp repeats and are highly inducible by Tax. Gel electrophoretic mobility shift assays, DNA transfection, and DNase I footprinting analyses indicated that the G- and C-rich sequences flanking the CRE motif are crucial for Tax-CREB-DNA ternary complex assembly and Tax transactivation but are not in direct contact with the Tax-CREB complex. These data show that Tax recruits CREB to form a multiprotein complex that specifically recognizes the viral 21-bp repeats. The expanded DNA binding specificity of Tax-CREB and the obligatory role the ternary Tax-CREB-DNA complex plays in transactivation reveal a novel mechanism for regulating the transcriptional activity of leucine zipper proteins like CREB.

scholarly journals Transfer of human T cell lymphotropic virus type I to human term trophoblast cells in vitro

1996 ◽  
Vol 77 (2) ◽  
pp. 369-374 ◽  
Author(s):  
X. Liu ◽  
V. Zachar ◽  
H. Hager ◽  
U. Koppelhus ◽  
P. Ebbesen
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Type I ◽  
Trophoblast Cells ◽  
Human T Cell

A 36-kilodalton cellular transcription factor mediates an indirect interaction of human T-cell leukemia/lymphoma virus type I TAX1 with a responsive element in the viral long terminal repeat

1990 ◽  
Vol 10 (8) ◽  
pp. 4192-4201
Author(s):  
S J Marriott ◽  
P F Lindholm ◽  
K M Brown ◽  
S D Gitlin ◽  
J F Duvall ◽  
...  
Keyword(s):  
T Cell ◽  
Long Terminal Repeat ◽  
Virus Type ◽  
Terminal Repeat ◽  
Type I ◽  
Indirect Interaction ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell ◽  
Responsive Element

The human T-cell leukemia/lymphoma virus type I (HTLV-I) trans activator, TAX1, interacts indirectly with a TAX1-responsive element, TRE-2, located at positions -117 to -163 in the viral long terminal repeat. This report describes the characterization of a 36-kilodalton (kDa) protein identified in HeLa nuclear extract which mediates the interaction of TAX1 with TRE-2. Purification of the protein was achieved by zinc chelate chromatography and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The renatured 36-kDa protein bound specifically to a TRE-2 oligonucleotide but not to nonfunctional base substitution mutant probes in a gel retardation assay. Renatured proteins of differing molecular weights were unable to form this complex. In addition, the 36-kDa protein specifically activated transcription from the HTLV-I promoter in vitro. Purified TAX1 protein formed a complex with the TRE-2 oligonucleotide in the presence of the 36-kDa protein, suggesting that indirect interaction of TAX1 with the viral long terminal repeat may be one of the mechanisms by which HTLV-I transcription is regulated.

In vitro selection of DNA elements highly responsive to the human T-cell lymphotropic virus type I transcriptional activator, Tax

1994 ◽  
Vol 14 (1) ◽  
pp. 456-462
Author(s):  
S Paca-Uccaralertkun ◽  
L J Zhao ◽  
N Adya ◽  
J V Cross ◽  
B R Cullen ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
In Vitro Selection ◽  
Type I ◽  
Mobility Shift ◽  
Camp Response Element ◽  
Response Element ◽  
Human T Cell ◽  
Dna Elements

The human T-cell lymphotropic virus type I (HTLV-I) transactivator, Tax, the ubiquitous transcriptional factor cyclic AMP (cAMP) response element-binding protein (CREB protein), and the 21-bp repeats in the HTLV-I transcriptional enhancer form a ternary nucleoprotein complex (L. J. Zhao and C. Z. Giam, Proc. Natl. Acad. Sci. USA 89:7070-7074, 1992). Using an antibody directed against the COOH-terminal region of Tax along with purified Tax and CREB proteins, we selected DNA elements bound specifically by the Tax-CREB complex in vitro. Two distinct but related groups of sequences containing the cAMP response element (CRE) flanked by long runs of G and C residues in the 5' and 3' regions, respectively, were preferentially recognized by Tax-CREB. In contrast, CREB alone binds only to CRE motifs (GNTGACG[T/C]) without neighboring G- or C-rich sequences. The Tax-CREB-selected sequences bear a striking resemblance to the 5' or 3' two-thirds of the HTLV-I 21-bp repeats and are highly inducible by Tax. Gel electrophoretic mobility shift assays, DNA transfection, and DNase I footprinting analyses indicated that the G- and C-rich sequences flanking the CRE motif are crucial for Tax-CREB-DNA ternary complex assembly and Tax transactivation but are not in direct contact with the Tax-CREB complex. These data show that Tax recruits CREB to form a multiprotein complex that specifically recognizes the viral 21-bp repeats. The expanded DNA binding specificity of Tax-CREB and the obligatory role the ternary Tax-CREB-DNA complex plays in transactivation reveal a novel mechanism for regulating the transcriptional activity of leucine zipper proteins like CREB.

In vitro activation of transcription by the human T-cell leukemia virus type I Tax protein

1992 ◽  
Vol 12 (5) ◽  
pp. 1986-1996
Author(s):  
M A Matthews ◽  
R B Markowitz ◽  
W S Dynan
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Cellular Proteins ◽  
Type I ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

The human T-cell leukemia virus type I (HTLV-I) regulatory protein Tax activates transcription of the proviral long terminal repeats and a number of cellular promoters. We have developed an in vitro system to characterize the mechanism by which Tax interacts with the host cell transcription machinery. Tax was purified from cells infected with a baculovirus expression vector. Addition of these Tax preparations to nuclear extracts from uninfected human T lymphocytes activated transcription of the HTLV-I long terminal repeat approximately 10-fold. Transcription-stimulatory activity copurified with the immunoreactive 40-kDa Tax polypeptide on gel filtration chromatography, and, as expected, the effect of recombinant Tax was diminished in HTLV-I-infected T-lymphocyte extracts containing endogenous Tax. Tax-mediated transactivation in vivo has been previously shown to require 21-bp-repeat Tax-responsive elements (TxREs) in the promoter DNA. Stimulation of transcription in vitro was also strongly dependent on these sequences. To investigate the mechanism of Tax transactivation, cellular proteins that bind the 21-bp-repeat TxREs were prepared by DNA affinity chromatography. Recombinant Tax markedly increased the formation of a specific host protein-DNA complex detected in an electrophoretic mobility shift assay. These data suggest that Tax activates transcription through a direct interaction with cellular proteins that bind to the 21-bp-repeat TxREs.

scholarly journals Overexpression of transforming growth factor-beta in transgenic mice carrying the human T-cell lymphotropic virus type I tax gene.

1991 ◽  
Vol 11 (10) ◽  
pp. 5222-5228 ◽  
Author(s):  
S J Kim ◽  
T S Winokur ◽  
H D Lee ◽  
D Danielpour ◽  
K Y Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Type I ◽  
Tgf Beta ◽  
Cell Leukemia ◽  
Human T Cell ◽  
Growth Factor Beta

Human T-cell lymphotropic virus type I (HTLV-I) has been associated with an adult form of T-cell leukemia as well as tropical spastic paraparesis, a neurodegenerative disease. Adult T-cell leukemia patients express high levels of the type 1 isoform of transforming growth factor-beta (TGF-beta 1), which is mediated by the effects of the HTLV-I Tax transactivator protein on the TGF-beta 1 promoter. To understand further the regulation of TGF-beta 1 expression by Tax, we examined its expression in transgenic mice carrying the HTLV-I tax gene. We show that tumors from these mice and other tissues, such as submaxillary glands and skeletal muscle, which express high levels of tax mRNA selectively express high levels of TGF-beta 1 mRNA and protein. Moreover, TGF-beta 1 significantly stimulated the incorporation of tritiated thymidine into one of three cell lines derived from neurofibromas of tax-transgenic mice, which suggests that the excessive production of TGF-beta 1 may play a role in tumorigenesis and that these mice may serve as a useful model for studying the biological effects of TGF-beta in vivo.

Evidence for autoantigens of Env/Tax proteins in human T cell leukemia virus type I Env-pX transgenic mice

1998 ◽  
Vol 41 (1) ◽  
pp. 101-109 ◽  
Author(s):  
Koushi Fujisawa ◽  
Kazuyoshi Okamoto ◽  
Hiroshi Asahara ◽  
Tomoko Hasunuma ◽  
Tetsuji Kobata ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
Virus Type ◽  
Leukemia Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus
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