Activation of HTLV-I Long Terminal Repeat by Stress-Inducing Agents and Protection of HTLV-I-Infected T-cells from Apoptosis by the Viral Tax Protein

Torgeman, Amram; Ben-Aroya, Zahi; Grunspan, Andrea; Zelin, Elena; Butovsky, Elena; Hallak, Mordechai; Löchelt, Martin; Flügel, Rolf M.; Livneh, Etta; Wolfson, Marina; Kedar, Igal; Aboud, Mordechai

doi:10.1006/excr.2001.5363

Cited by 34 publications

(67 citation statements)

References 48 publications

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Section: Introductionmentioning

confidence: 73%

“…In previous studies, we have demonstrated such a TPA-induced downregulation of cPKCs and nPKCs in the Jurkat human T-cell line (Mor-Vaknin et al, 1997;Torgeman et al, 2001a). We have also shown that TPA activates the expression of HTLV-I and induces apoptosis in these cells (Torgeman et al, 2001a). However, we have noted that both of these effects start only when the cells are already depleted of the TPA-responsive PKCs, or if PKC activity is blocked by specific inhibitors (Mor-Vaknin et al, 1997;Torgeman et al, 2001a, b).…”

Section: Introductionmentioning

confidence: 83%

“…Although most of the TPA-induced biological effects are exerted through PKC-associated pathways, we have previously shown that TPA stimulates HTLV-I LTR expression (Mor-Vaknin et al, 1997;Torgeman et al, 1999;Torgeman et al, 2001b) and induces apoptosis (Torgeman et al, 2001a) in Jurkat and certain other human T-cell lines, as well as in primary human lymphocytes (Torgeman et al, 2001a), by PKC-independent mechanisms. Therefore, we investigated whether the TPA-induced stimulation of p21 WAF-1 required PKC activity by testing this effect in the presence of the PKC-specific inhibitor bisindolylmaleimide GF 109203X (BI) (Hingorani et al, 2000;Toullec et al, 1991).…”

Section: Tpa-induced Pkc-dependent Activation Of P21 Waf-1 In Htlv-i mentioning

confidence: 99%

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Role of protein kinase C and the Sp1-p53 complex in activation of p21WAF-1 expression by 12-O-tetradecanoylphorbol-13-acetate in human T cells

Schavinsky-Khrapunsky

Huleihel

Aboud

et al. 2003

Oncogene

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Previous reports have shown that, in certain cell types, p21 WAF-1 , which plays a central role in cell proliferation, can be activated by HTLV-I Tax protein and by TPA. Tax and TPA are also known to stimulate HTLV-I gene expression. Since cell proliferation has a major impact on HTLV-I replication, it was of interest to investigate their effect on p21 WAF-1 in human T cells, which are the main target of HTLV-I in human infection. This study demonstrates that p21 WAF-1 is activated in such cells by both factors, each acting through a different mechanism that does not influence the other. The effect of TPA is shown to require PKC activity. Notably, however, examination of different PKC isoforms revealed that PKC-a and PKC-e stimulated p21 WAF-1 expression, whereas PKC-g was rather inhibitory and PKC-b1 and b2 were ineffective. All these isoforms were found to be activated by TPA in the employed T cells, but this apparent paradox was resolved by the observation that when coexpressed together in these cells, the stimulatory PKCs override the inhibitory isoform. Further experiments demonstrated that the PKC-induced p21 WAF-1 activation was mediated by binding of Sp1-p53 complex to the second most upstream of the six Sp1 recognition sites present in its promoter and that this effect did not require the cooperation of an p53-binding site.

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Section: Introductionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 83%

Section: Tpa-induced Pkc-dependent Activation Of P21 Waf-1 In Htlv-i mentioning

confidence: 99%

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Role of protein kinase C and the Sp1-p53 complex in activation of p21WAF-1 expression by 12-O-tetradecanoylphorbol-13-acetate in human T cells

Schavinsky-Khrapunsky

Huleihel

Aboud

et al. 2003

Oncogene

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“…Oncogenes such as Myc, E1A and E2F-1 all demonstrate such duality, and Tax may share this property. There is evidence that Tax protects cells from stress-induced cell cycle arrest or apoptosis (Copeland et al, 1994;Brauweiler et al, 1997;Torgeman et al, 2001;Kasai and Jeang, 2004), but can also sensitize cells to stress-induced apoptosis (Chlichlia et al, 1995(Chlichlia et al, , 1997(Chlichlia et al, , 2002Kao et al, 2000;Kasai and Jeang, 2004). This duality may be because transforming insults induce countervailing responses by the cell's tumor suppressors, which often manifest as cell cycle arrest and/or apoptosis.…”

Section: Proliferation Versus Apoptosismentioning

confidence: 99%

Molecular mechanisms of cellular transformation by HTLV-1 Tax

2005

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“…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]. In addition, Tax might ensure protection against apoptosis in the presence of various stress-inducing agents [Torgeman et al, 2001]. Relevant to this work it should be noted that all the experimental approaches concerning the capability of HTLV-1 and, in particular, of Tax to regulate apoptotic cell death did not consider time as a variable which could influence this dual, regulatory action.…”

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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Activation of HTLV-I Long Terminal Repeat by Stress-Inducing Agents and Protection of HTLV-I-Infected T-cells from Apoptosis by the Viral Tax Protein

Cited by 34 publications

References 48 publications

Role of protein kinase C and the Sp1-p53 complex in activation of p21WAF-1 expression by 12-O-tetradecanoylphorbol-13-acetate in human T cells

Role of protein kinase C and the Sp1-p53 complex in activation of p21WAF-1 expression by 12-O-tetradecanoylphorbol-13-acetate in human T cells

Molecular mechanisms of cellular transformation by HTLV-1 Tax

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

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