scholarly journals Human T-cell lymphotropic virus type I-transformed T-cells have a partial defect in ceramide synthesis in response to N-(4-hydroxyphenyl)retinamide

2005 ◽  
Vol 392 (1) ◽  
pp. 231-239 ◽  
Author(s):  
Nadine Darwiche ◽  
Ghada Abou-Lteif ◽  
Tarek Najdi ◽  
Lina Kozhaya ◽  
Ahmad Abou Tayyoun ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Growth Inhibition ◽  
Virus Type ◽  
De Novo ◽  
Type I ◽  
De Novo Synthesis ◽  
Human T Cell ◽  
Ceramide Synthesis ◽  
Malignant T Cells

Treatment with the synthetic retinoid HPR [N-(4-hydroxyphenyl)-retinamide] causes growth arrest and apoptosis in HTLV-I (human T-cell lymphotropic virus type-I)-positive and HTLV-I-negative malignant T-cells [8]. It was observed that HPR-mediated growth inhibition was associated with ceramide accumulation only in HTLV-I-negative cells. The aim of the present study was to investigate the mechanism by which HPR differentially regulates ceramide metabolism in HTLV-I-negative and HTLV-I-positive malignant T-cells. Clinically achievable concentrations of HPR caused early dose-dependent increases in ceramide levels only in HTLV-I-negative cells and preceded HPR-induced growth suppression. HPR induced de novo synthesis of ceramide in HTLV-I-negative, but not in HTLV-I-positive, cells. Blocking ceramide glucosylation in HTLV-I-positive cells, which leads to accumulation of endogenous ceramide, rendered these cells more sensitive to HPR. Exogenous cell-permeant ceramides that function partially by generating endogenous ceramide induced growth suppression in all tested malignant lymphocytes, were consistently found to be less effective in HTLV-I-positive cells confirming their defect in de novo ceramide synthesis. Owing to its multipotent activities, the HTLV-I-encoded Tax protein was suspected to inhibit ceramide synthesis. Tax-transfected Molt-4 and HELA cells were less sensitive to HPR and C6-ceramide mediated growth inhibition respectively and produced lower levels of endogenous ceramide. Together, these results indicate that HTLV-I-positive cells are defective in de novo synthesis of ceramide and that therapeutic modalities that bypass this defect are more likely to be successful.

scholarly journals Human T-cell lymphotropic virus type I-transformed T-cells have a partial defect in ceramide synthesis in response to N-(4-hydroxyphenyl)retinamide

2012 ◽  
Vol 444 (3) ◽  
pp. 619-619
Author(s):  
N. Darwiche ◽  
G. Abou-Lteif ◽  
T. Najdi ◽  
L. Kozhaya ◽  
A. Abou Tayoun ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Type ◽  
Type I ◽  
Human T Cell ◽  
Ceramide Synthesis

scholarly journals Activation of T cell-derived lymphokine genes in T cells and fibroblasts: effects of human T cell leukemia virus type I p40xprotein and bovine papilloma virus encoded E2 protein

1988 ◽  
Vol 16 (14) ◽  
pp. 6547-6566 ◽  
Author(s):  
Shoichiro Miyatake ◽  
Motoharu Seiki ◽  
Rene DeWaal Malefijt ◽  
Toshio Heike ◽  
Jun-ichi Fujisawa ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Type I ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Papilloma Virus ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Protective effect of interferon ? on human T cell leukaemia virus type I infection of CD4+ T cells isolated from human cord blood

1993 ◽  
Vol 37 (2) ◽  
pp. 97-104 ◽  
Author(s):  
Beatrice Macchi ◽  
Isabella Faraoni ◽  
Antonio Mastino ◽  
Chiara D'Onofrio ◽  
Gianna Romeo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Protective Effect ◽  
Cord Blood ◽  
Virus Type ◽  
Cell Leukaemia ◽  
Type I ◽  
Human Cord Blood ◽  
Leukaemia Virus ◽  
Human T Cell

scholarly journals Human T Cell Lymphotropic Virus Type I (HTLV-I)-Specific CD4+T Cells: Immunodominance Hierarchy and Preferential Infection with HTLV-I

2004 ◽  
Vol 172 (3) ◽  
pp. 1735-1743 ◽  
Author(s):  
Peter K. C. Goon ◽  
Tadahiko Igakura ◽  
Emmanuel Hanon ◽  
Angelina J. Mosley ◽  
Anna Barfield ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Type ◽  
Cd4 T Cells ◽  
Type I ◽  
Human T Cell

scholarly journals p53 functional impairment and high p21waf1/cip1 expression in human T- cell lymphotropic/leukemia virus type I-transformed T cells

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1551-1560 ◽  
Author(s):  
A Cereseto ◽  
F Diella ◽  
JC Mulloy ◽  
A Cara ◽  
P Michieli ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Type ◽  
Cell Transformation ◽  
Leukemia Virus ◽  
Type I ◽  
Wild Type ◽  
Human T Cell ◽  
Wild Type P53

Abstract Human T-cell lymphotropic/leukemia virus type I (HTLV-I) is associated with T-cell transformation both in vivo and in vitro. Although some of the mechanisms responsible for transformation remain unknown, increasing evidence supports a direct role of viral as well as dysregulated cellular proteins in transformation. We investigated the potential role of the tumor suppressor gene p53 and of the p53- regulated gene, p21waf1/cip1 (wild-type p53 activated fragment 1/cycling dependent kinases [cdks] interacting protein 1), in HTLV-I- infected T cells. We have found that the majority of HTLV-I-infected T cells have the wild-type p53 gene. However, its function in HTLV-I- transformed cells appears to be impaired, as shown by the lack of appropriate p53-mediated responses to ionizing radiation (IR). Interestingly, the expression of the p53 inducible gene, p21waf1/cip1, is elevated at the messenger ribonucleic acid and protein levels in all HTLV-I-infected T-cell lines examined as well as in Taxl-1, a human T- cell line stably expressing Tax. Additionally, Tax induces upregulation of a p21waf1/cip1 promoter-driven luciferase gene in p53 null cells, and increases p21waf1/cip1 expression in Jurkat T cells. These findings suggest that the Tax protein is at least partially responsible for the p53-independent expression of p21waf1/cip1 in HTLV-I-infected cells. Dysregulation of p53 and p21waf1/cip1 proteins regulating cell-cycle progression, may represent an important step in HTLV-I-induced T-cell transformation.

scholarly journals p53 functional impairment and high p21waf1/cip1 expression in human T- cell lymphotropic/leukemia virus type I-transformed T cells

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1551-1560 ◽  
Author(s):  
A Cereseto ◽  
F Diella ◽  
JC Mulloy ◽  
A Cara ◽  
P Michieli ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Type ◽  
Cell Transformation ◽  
Leukemia Virus ◽  
Type I ◽  
Wild Type ◽  
Human T Cell ◽  
Wild Type P53

Human T-cell lymphotropic/leukemia virus type I (HTLV-I) is associated with T-cell transformation both in vivo and in vitro. Although some of the mechanisms responsible for transformation remain unknown, increasing evidence supports a direct role of viral as well as dysregulated cellular proteins in transformation. We investigated the potential role of the tumor suppressor gene p53 and of the p53- regulated gene, p21waf1/cip1 (wild-type p53 activated fragment 1/cycling dependent kinases [cdks] interacting protein 1), in HTLV-I- infected T cells. We have found that the majority of HTLV-I-infected T cells have the wild-type p53 gene. However, its function in HTLV-I- transformed cells appears to be impaired, as shown by the lack of appropriate p53-mediated responses to ionizing radiation (IR). Interestingly, the expression of the p53 inducible gene, p21waf1/cip1, is elevated at the messenger ribonucleic acid and protein levels in all HTLV-I-infected T-cell lines examined as well as in Taxl-1, a human T- cell line stably expressing Tax. Additionally, Tax induces upregulation of a p21waf1/cip1 promoter-driven luciferase gene in p53 null cells, and increases p21waf1/cip1 expression in Jurkat T cells. These findings suggest that the Tax protein is at least partially responsible for the p53-independent expression of p21waf1/cip1 in HTLV-I-infected cells. Dysregulation of p53 and p21waf1/cip1 proteins regulating cell-cycle progression, may represent an important step in HTLV-I-induced T-cell transformation.

NF-κB activity in T cells stably expressing the Tax protein of human T cell lymphotropic virus type I

Virology ◽  
1991 ◽  
Vol 184 (2) ◽  
pp. 553-562 ◽  
Author(s):  
Judith Lacoste ◽  
Lucie Cohen ◽  
John Hiscott
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Type ◽  
Type I ◽  
Tax Protein ◽  
Human T Cell

scholarly journals Human T cell leukemia virus type I Tax enhances IL-4 gene expression in T cells

2001 ◽  
Vol 31 (9) ◽  
pp. 2623-2632 ◽  
Author(s):  
Min Li-Weber ◽  
Marco Giaisi ◽  
Katerina Chlichlia ◽  
Khashayarsha Khazaie ◽  
Peter H. Krammer
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Type I ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals Human T-cell leukemia virus type I Tax associates with and is negatively regulated by the NF-kappa B2 p100 gene product: implications for viral latency

1994 ◽  
Vol 14 (2) ◽  
pp. 1374-1382
Author(s):  
C Béraud ◽  
S C Sun ◽  
P Ganchi ◽  
D W Ballard ◽  
W C Greene
Keyword(s):  
T Cells ◽  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Human T Cell

Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent of the adult T-cell leukemia, an aggressive and often fatal malignancy of activated human CD4 T cells. HTLV-I encodes an essential 40-kDa protein termed Tax that not only transactivates the long terminal repeat of this retrovirus but also induces an array of cellular genes. Tax-mediated transformation of T cells likely involves the deregulated expression of various cellular genes that normally regulate lymphocyte growth produced by altered activity of various endogenous host transcription factors. In particular, Tax is capable of modulating the expression or activity of various host transcription factors, including members of the NF-kappa B/Rel and CREB/ATF families, as well as the cellular factors HEB-1 and p67SRF. An additional distinguishing characteristic of HTLV-I infection is the profound state of viral latency that is present in circulating primary leukemic T cells. In this study, we demonstrate that HTLV-I Tax can physically associate with p100, the product of the Rel-related NF-kappa B2 gene, both in transfected cells and in HTLV-I-infected leukemic T-cell lines. Furthermore, the physical interaction of Tax with p100 leads to the inhibition of Tax-induced activation of the HTLV-I and human immunodeficiency virus type 1 long terminal repeats, reflecting p100-mediated cytoplasmic sequestration of the normally nuclearly expressed Tax protein. In contrast, a mutant of Tax that selectively fails to activate nuclear NF-kappa B expression does not associate with p100. Together, these results suggest that the cytoplasmic interplay of Tax and p100 may play an important role in the initiation and maintenance of HTLV-1 latency observed in adult T-cell leukemia.

Sign in / Sign up

Export Citation Format

Share Document