scholarly journals NF-κB Signaling Pathway Governs TRAIL Gene Expression and Human T-cell Leukemia Virus-I Tax-induced T-cell Death

2001 ◽  
Vol 276 (44) ◽  
pp. 40385-40388 ◽  
Author(s):  
Isis Rivera-Walsh ◽  
Michael Waterfield ◽  
Gutian Xiao ◽  
Abraham Fong ◽  
Shao-Cong Sun
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
T Cell ◽  
Signaling Pathway ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Human T-Cell Leukemia Virus Type 1 Tax Enhances Serum Response Factor DNA Binding and Alters Site Selection

2007 ◽  
Vol 81 (11) ◽  
pp. 6089-6098 ◽  
Author(s):  
Heather Y. Winter ◽  
Susan J. Marriott
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Serum Response Factor ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
Serum Response

ABSTRACT Human T-cell leukemia virus type I (HTLV-1) is the etiological agent of adult T-cell leukemia. The viral transforming protein Tax regulates the transcription of viral and cellular genes by interacting with cellular transcription factors and coactivators. The effects of Tax on cellular gene expression have an important impact on HTLV-1-mediated cellular transformation. Expression of the c-fos cellular oncogene is regulated by serum response factor (SRF), and Tax is known to induce c-fos gene expression by activating SRF-responsive transcription. SRF activates cellular gene expression by binding to a consensus DNA sequence (CArG box) located within a serum response element (SRE). Since SRF activates transcription of many growth regulatory genes, this pathway is likely to have a significant impact on Tax-mediated transformation. Here we demonstrate that Tax interacts with SRF and enhances the binding of SRF to SREs located in the c-fos, Nur77, and viral promoters. Also, we establish that in the presence of Tax, SRF selects more divergent CArG box sequences than in the absence of Tax, revealing a novel mechanism for regulating SRF-responsive gene expression. Finally, increased association of SRF with chromatin and specific promoters was observed in Tax-expressing cells, correlating with increased c-fos and Nur77 mRNA levels in Tax-expressing cells. These results suggest that Tax activates SRF-responsive transcription by enhancing its binding affinity to multiple different SRE sequences.

Regulation of Human T-Cell Leukemia Virus Type 1 Gene Expression by Sp1 and Sp3 Interaction with TRE-1 Repeat III

2006 ◽  
Vol 25 (5) ◽  
pp. 262-276 ◽  
Author(s):  
Jing Yao ◽  
Christian Grant ◽  
Edward Harhaj ◽  
Michael Nonnemacher ◽  
Timothy Alefantis ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Rex transregulation of human T-cell leukemia virus type II gene expression.

1991 ◽  
Vol 65 (1) ◽  
pp. 405-414 ◽  
Author(s):  
J H Kim ◽  
P A Kaufman ◽  
S M Hanly ◽  
L T Rimsky ◽  
W C Greene
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Type Ii ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Suppression of Human T-cell Leukemia Virus I Gene Expression by Pokeweed Antiviral Protein

2009 ◽  
Vol 284 (45) ◽  
pp. 31453-31462 ◽  
Author(s):  
Sheila Mansouri ◽  
Gunjan Choudhary ◽  
Paulina M. Sarzala ◽  
Lee Ratner ◽  
Katalin A. Hudak
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Pokeweed Antiviral Protein ◽  
Cell Leukemia ◽  
Antiviral Protein ◽  
Human T Cell ◽  
T Cell Leukemia Virus ◽  
I Gene

scholarly journals Activation of Human T-Cell Leukemia Virus Type 1tax Gene Expression in Chronically Infected T Cells

1998 ◽  
Vol 72 (7) ◽  
pp. 6264-6270 ◽  
Author(s):  
Hsin-Ching Lin ◽  
Charlene S. Dezzutti ◽  
Renu B. Lal ◽  
Arnold B. Rabson
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Virus Type ◽  
Phorbol Esters ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACT Expression of human T-cell leukemia virus type 1 (HTLV-1) is regulated both by the HTLV-1 Tax transactivator and by cellular transcriptional factors binding to the viral long terminal repeat (LTR), suggesting that cellular signals may play a role in regulating viral expression. Treatment of cells chronically infected with HTLV-1, which express low levels of HTLV-1 RNAs and Tax protein, with phorbol esters (i.e., phorbol12-myristate 13- acetate [PMA]), phytohemagglutinin (PHA), sodium butyrate, or combinations of cytokines resulted in induction of HTLV- 1 gene expression. PMA or PHA treatment following cotransfection of HTLV-1 Tax expression plasmids resulted in synergistic activation of HTLV-1 LTR-directed gene expression, apparently involving tyrosine ki- nase- mediated pathways. These results suggest that cellular activation stimuli may cooperate with HTLV-1 Tax to enhance expression of integrated HTLV-1 genomes and thus may play a role in the pathogenesis of HTLV-1 disease.

scholarly journals SIRT1 Suppresses Human T-Cell Leukemia Virus Type 1 Transcription

2015 ◽  
Vol 89 (16) ◽  
pp. 8623-8631 ◽  
Author(s):  
Hei-Man Vincent Tang ◽  
Wei-Wei Gao ◽  
Chi-Ping Chan ◽  
Yun Cheng ◽  
Jian-Jun Deng ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACTHuman T-cell leukemia virus type 1 (HTLV-1)-associated diseases are poorly treatable, and HTLV-1 vaccines are not available. High proviral load is one major risk factor for disease development. HTLV-1 encodes Tax oncoprotein, which activates transcription from viral long terminal repeats (LTR) and various types of cellular promoters. Counteracting Tax function might have prophylactic and therapeutic benefits. In this work, we report on the suppression of Tax activation of HTLV-1 LTR by SIRT1 deacetylase. The transcriptional activity of Tax on the LTR was largely ablated when SIRT1 was overexpressed, but Tax activation of NF-κB was unaffected. On the contrary, the activation of the LTR by Tax was boosted when SIRT1 was depleted. Treatment of cells with resveratrol shunted Tax activity in a SIRT1-dependent manner. The activation of SIRT1 in HTLV-1-transformed T cells by resveratrol potently inhibited HTLV-1 proviral transcription and Tax expression, whereas compromising SIRT1 by specific inhibitors augmented HTLV-1 mRNA expression. The administration of resveratrol also decreased the production of cell-free HTLV-1 virions from MT2 cells and the transmission of HTLV-1 from MT2 cells to uninfected Jurkat cells in coculture. SIRT1 associated with Tax in HTLV-1-transformed T cells. Treatment with resveratrol prevented the interaction of Tax with CREB and the recruitment of CREB, CRTC1, and p300 to Tax-responsive elements in the LTR. Our work demonstrates the negative regulatory function of SIRT1 in Tax activation of HTLV-1 transcription. Small-molecule activators of SIRT1 such as resveratrol might be considered new prophylactic and therapeutic agents in HTLV-1-associated diseases.IMPORTANCEHuman T-cell leukemia virus type 1 (HTLV-1) causes a highly lethal blood cancer or a chronic debilitating disease of the spinal cord. Treatments are unsatisfactory, and vaccines are not available. Disease progression is associated with robust expression of HTLV-1 genes. Suppressing HTLV-1 gene expression might have preventive and therapeutic benefits. It is therefore critical that host factors controlling HTLV-1 gene expression be identified and characterized. This work reveals a new host factor that suppresses HTLV-1 gene expression and a natural compound that activates this suppression. Our findings not only provide new knowledge of the host control of HTLV-1 gene expression but also suggest a new strategy of using natural compounds for prevention and treatment of HTLV-1-associated diseases.

scholarly journals Epigenetic Regulation of Human T-Cell Leukemia Virus Gene Expression

2021 ◽  
Vol 10 (1) ◽  
pp. 84
Author(s):  
Lee Ratner
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
T Cell ◽  
Histone Modifications ◽  
Leukemia Virus ◽  
Nucleosome Positioning ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Viral and cellular gene expression are regulated by epigenetic alterations, including DNA methylation, histone modifications, nucleosome positioning, and chromatin looping. Human T-cell leukemia virus type 1 (HTLV-1) is a pathogenic retrovirus associated with inflammatory disorders and T-cell lymphoproliferative malignancy. The transforming activity of HTLV-1 is driven by the viral oncoprotein Tax, which acts as a transcriptional activator of the cAMP response element-binding protein (CREB) and nuclear factor kappa B (NFκB) pathways. The epigenetic effects of Tax and the induction of lymphoproliferative malignancy include alterations in DNA methylation and histone modifications. In addition, alterations in nucleosome positioning and DNA looping also occur in HTLV-1-induced malignant cells. A mechanistic definition of these effects will pave the way to new therapies for HTLV-1-associated disorders.

scholarly journals Phosphorylation of the Human T-Cell Leukemia Virus Type 1 Transactivator Tax on Adjacent Serine Residues Is Critical for Tax Activation

1999 ◽  
Vol 73 (1) ◽  
pp. 738-745 ◽  
Author(s):  
Françoise Bex ◽  
Kathy Murphy ◽  
Ruddy Wattiez ◽  
Arsène Burny ◽  
Richard B. Gaynor
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Leukemia Virus ◽  
Nuclear Bodies ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

ABSTRACT The Tax transactivator protein of human T-cell leukemia virus type 1 (HTLV-1) plays a central role in the activation of viral gene expression. In addition, Tax is capable of activating the expression of specific cellular genes and is involved in the transformation of T-lymphocytes resulting in the development of adult T-cell leukemia. Tax is a phosphoprotein that colocalizes in nuclear bodies with RNA polymerase II, splicing complexes, and specific transcription factors including members of the ATF/CREB and NF-κB families. In this study, we identified adjacent serine residues at positions 300 and 301 in the carboxy terminus of Tax as the major sites for phosphorylation. Phosphorylation of at least one of these serine residues is required for Tax localization in nuclear bodies and for Tax-mediated activation of gene expression via both the ATF/CREB and NF-κB pathways. Introduction of amino acid substitutions which are phosphoserine mimetics at positions 300 and 301 restored the ability of a phosphorylation-defective Tax mutant to form nuclear bodies and to activate gene expression. These studies define sites for regulatory phosphorylation events in Tax which are critical for its ability to activate gene transcription.

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