Inhibition of Apoptosis in T Cells Expressing Human T Cell Leukemia Virus Type I Tax

Copeland, Karen F.T.; Haaksma, Anthonius G.M.; Goudsmit, Jaap; Krammer, Peter H.; Heeney, Jonathan L.

doi:10.1089/aid.1994.10.1259

Cited by 110 publications

(83 citation statements)

References 54 publications

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“…Although evidence suggests that Tax either induces apoptosis or sensitizes cells to apoptotic death, there are also several reports showing an inhibition of apoptosis by Tax or HTLV-1 infection (Brauweiler et al, 1997;Copeland et al, 1994;Tsukahara et al, 1999;Mulloy et al, 1998). It has been reported that apoptosis induced by UV irradiation is inhibited in HTLV-1 infected cells (Brauweiler et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…These studies con¯ict with our results however, since infected cell lines were used in those studies, the inhibition of apoptosis may not have been Taxspeci®c. Tax also inhibited apoptosis induced by anti-APO-1 treatment (Copeland et al, 1994) or IL-2 withdrawal (Tsukahara et al, 1999). Tax has been shown to repress bax expression in vitro (Brauweiler et al, 1997), activate bcl-xl expression (Tsukahara et al, 1999) and inactivate p53 function (Mulloy et al, 1998), each of which suggests a role for Tax in inhibition of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Tax has been shown to induce apoptosis in a variety of systems (Chen et al, 1997;Chlichlia et al, 1995Chlichlia et al, ,1997Fujita and Shiku, 1995;Hall et al, 1998;Kitajima et al, 1996;Yamada et al, 1994), consistent with its ability to reduce DNA repair. However, in other reports Tax has been shown to inhibit apoptosis (Brauweiler et al, 1997;Copeland et al, 1994;Tsukahara et al, 1999;Mulloy et al, 1998), supporting its role as a transforming protein and inducer of T cell proliferation. The ability of Tax to activate or inhibit apoptosis may depend on the method used to induce apoptosis.…”

Section: Introductionmentioning

confidence: 86%

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HTLV-1 Tax protein sensitizes cells to apoptotic cell death induced by DNA damaging agents

2000

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Transient HTLV-1 Tax expression suppresses cellular nucleotide excision repair, and this e ect correlates with Tax transactivation of the proliferating cell nuclear antigen promoter. The inability to repair DNA damage typically induces apoptotic cell death. Therefore, we investigated the e ect of Tax-mediated suppression of DNA repair on apoptosis in stable Tax-expressing cells. Constitutive Tax expression reduced cellular nucleotide excision repair activity compared with parental and control cells. Tax-expressing cells were also more sensitive to apoptosis induced by DNA damaging agents than control cells. Even though Tax-expressing cells displayed reduced DNA repair, they showed increased DNA replication following UV damage. These results suggest that Tax suppresses the cell's ability to repair DNA damage and stimulates DNA replication even in the presence of damage. The inability to repair DNA damage is likely to stimulate apoptotic cell death in the majority of Tax-expressing cells while the ability to promote DNA replication may also allow the survival of a small population of cells. We propose that together these e ects contribute to the monoclonal nature and low e ciency of HTLV-1 transformation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 86%

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HTLV-1 Tax protein sensitizes cells to apoptotic cell death induced by DNA damaging agents

2000

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“…[14][15][16][17][18] Such a function of Tax prompts us to investigate the transcriptional regulation of survivin in HTLV-I-infected and Taxexpressing T cells. We previously showed that IL-2-dependent CTLL-2 cell lines that express Tax are resistant to apoptosis induced in the absence of IL-2.…”

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confidence: 99%

Transcriptional activation of survivin through the NF‐κB pathway by human T‐cell leukemia virus type I tax

Kawakami

Tomita

Matsuda

et al. 2005

Intl Journal of Cancer

142

112

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Survivin, a unique member of the inhibitor of apoptosis protein family, is overexpressed in many cancers and considered to play an important role in oncogenesis. We previously reported the survivin expression profile in ATL, a CD4-positive T-cell malignancy caused by HTLV-I. HTLV-I Tax is thought to play an important role in immortalization of T cells. We have shown also that the expression of Tax protected the mouse T-cell line CTLL-2 against apoptosis induced by deprivation of IL-2 and converted its growth from being IL-2 dependent to being IL-2 independent through the NF-kB pathway. In our study, we demonstrate that constitutive expression of survivin was associated with resistance to apoptosis after IL-2 deprivation in Tax-expressing CTLL-2 cells. Transient transfection assays showed that survivin promoter was transactivated by Tax, via the activation of NF-kB. Pharmacological NFkB inhibition resulted in suppression of survivin expression and caused apoptosis of Tax-expressing CTLL-2 cells. Our findings suggest that activated NF-kB signaling contributes directly to malignant progression of ATL by preventing apoptosis, acting through the prosurvival protein survivin. ' 2005 Wiley-Liss, Inc.

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“…It has been hypothesized that induction of apoptosis might depend on nuclear expression of the CREB-binding protein (CBP)/p300-binding domain of the HTLV-1 transactivator Tax [Nicot and Harrod, 2000]. Conversely, it has been shown that HTLV-1-expressing human T-cell lines showed reduced susceptibility to anti-Fas [Copeland et al, 1994], and to TNFa stimulation [Yang et al, 2002]. This resistance to apoptosis might be due to the activation of NF-kB via Tax protein in HTLV-1 infected cells [Kawakami et al, 1999], to Tax-induced expression of anti-apoptotic genes [Brauweiler et al, 1997;Mori et al, 2001] and should involve p21 [Kawata et al, 2003].…”

Section: Introductionmentioning

confidence: 99%

Modulation of apoptosis during HTLV‐1‐mediated immortalization process in vitro

Matteucci

Balestrieri

Macchi

et al. 2004

Journal of Medical Virology

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Suppression of apoptosis has been proposed as a mechanism involved in the transforming action of human T-cell leukemia/lymphotropic virus type-1 (HTLV-1). However, there is evidence that HTLV-1 and its protein Tax also induce apoptosis. To resolve this apparent paradox, apoptosis was monitored in primary cultures of peripheral blood lymphocytes (PBLs) from healthy donors, following HTLV-1 infection in vitro. High levels of apoptosis in HTLV-1 infected cultures during the first weeks after infection were detected. Apoptosis was not related to the presence of uninfected cells, as revealed by a fluorescence in situ hybridization assay. Successively, a progressive decrease in apoptosis in infected cultures going towards immortalization, was observed. When IL-2 in the medium was replaced by IL-4, allowing the cells to be efficiently infected by HTLV-1 but not immortalized, apoptosis levels tended to increase, instead of decreasing, with the ongoing time. The caspase cascade was remarkably activated in PBLs recently infected in vitro by HTLV-1, but apoptosis was only partly reduced by caspase inhibitors. Even if spontaneous apoptosis was relatively low in long-term cultures of PBLs immortalized by HTLV-1 in vitro, Fas death-receptor expression and function were well conserved. These observations provide a new rationale for explaining the dual effect of HTLV-1 in controlling apoptosis.

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Inhibition of Apoptosis in T Cells Expressing Human T Cell Leukemia Virus Type I Tax

Cited by 110 publications

References 54 publications

HTLV-1 Tax protein sensitizes cells to apoptotic cell death induced by DNA damaging agents

HTLV-1 Tax protein sensitizes cells to apoptotic cell death induced by DNA damaging agents

Transcriptional activation of survivin through the NF‐κB pathway by human T‐cell leukemia virus type I tax

Modulation of apoptosis during HTLV‐1‐mediated immortalization process in vitro

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