Life, Death, and Tax: Role of HTLV-I Oncoprotein in Genetic Instability and Cellular Transformation

Jeang, Kuan‐Teh; Giam, Chou-Zen; Majone, Franca; Aboud, Mordechai

doi:10.1074/jbc.r400009200

Cited by 160 publications

(176 citation statements)

References 110 publications

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“…STLV-3 provirus , and a recent report convincingly proved that a number of agile mangabeys that live in Cameroon are naturally co-infected with STLV-1 and STLV-3 (Courgnaud et al, 2004). The HTLV-1-mediated cellular transformation is a multistep process that is made possible by the pleiotropic effects of the viral Tax1 protein (Jeang et al, 2004). Several lines of evidence have demonstrated a pivotal role for the HTLV-1 Tax protein in the immortalization or transformation of the HTLV-1-infected cells.…”

Section: Discussionmentioning

confidence: 95%

“…Nevertheless, the precise mechanism by which Tax initiates the malignant process is still a matter of investigation, but likely involves several points of transcriptional and/or post-transcriptional deregulation in the infected T lymphocytes (Jeang et al, 2004). More recently, the presence of a PDZ-binding domain in the C-terminus end of Tax1 has also been suggested to be involved in the ability of the viral protein to elicit cell transformation (Endo et al, 2002).…”

Section: Characterization Of the Htlv/stlv-3 Tax Proteinmentioning

confidence: 99%

“…Tax1 possesses an oncogenic potential and is responsible for the cell transformation both in vivo and in vitro (Jeang et al, 2004). Interestingly, even if it possesses an ORF corresponding to the tax gene, the STLV-3 pX region organization is different from that of PTLV-1 and PTLV-2, with the absence of ORFs that would be equivalent to p12, p13 and p30 (Van Brussel et al, 1996;Meertens et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…At the amino-acid level, the available putative human HTLV-3 Tax protein sequence (Tax3 H ) possesses only 75 and 79% similarity with HTLV-1 and HTLV-2 Tax proteins (Tax1 and Tax2) (Wolfe et al, 2005), but 97% identity with the putative simian STLV-3 602 Tax protein. Given the recent discovery of HTLV-3 (Calattini et al, 2005;Wolfe et al, 2005), the large and increasing number of simian species infected with STLV-3 and the known transactivating ability of Tax proteins (Jeang et al, 2004), the Tax3 molecular properties needed to be investigated. The aims of the present study were therefore to assess the Tax3 protein for (a) expression in vivo, (b) transactivation ability through the NF-kB and Cyclic AMP Response Element Binding (CREB) pathways and further transformation of human and simian cells in vivo, (c) mediation capacity for transcription of the autologous LTR in spite of lacking the distal TRE sequence (Van Brussel et al, 1997;Meertens et al, 2002Van Dooren et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

et al. 2006

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Human T-cell leukemia virus and simian T-cell leukemia virus (STLV) form the primate T-cell lymphotropic viruses group. Human T-cell leukemia virus type 1 and type 2 (HTLV-1 and HTLV-2) encode the Tax viral transactivator (Tax1 and Tax2, respectively). Tax1 possesses an oncogenic potential and is responsible for cell transformation both in vivo and in vitro. We and others have recently discovered the existence of human Tcell lymphotropic virus type 3. However, there is currently no evidence for the presence of a Tax protein in HTLV-3-infected individuals. We show that the serum of an HTLV-3 asymptomatic carrier and the sera of two STLV-3-infected monkeys contain specific anti-Tax3 antibodies. We also show that tax3 mRNA is present in the PBMCs obtained from an STLV-3-infected monkey, demonstrating that Tax3 is expressed in vivo. We further demonstrate that Tax3 intracellular localization is very similar to that of Tax1 and that Tax3 binds to both CBP and p300 coactivators. Using purified Tax3, we show that the protein increases transcription from a 4TxRE G-free cassette plasmid in an in vitro transcription assay. In all cell types tested, including transiently transfected lymphocytes, Tax3 activates its own promoter STLV-3 long terminal repeat (LTR), which contains only two Tax Responsive Elements (TREs), and activates also HTLV-1 and HTLV-2 LTRs. In addition, Tax3 also activates the NF-jB pathway. We also show that Tax3 possesses a PDZ-binding sequence at its C-terminal end. Our results demonstrate that Tax3 is a transactivator, and that its properties are more similar to that of Tax1, rather than of Tax2. This suggests the possible occurrence of lymphoproliferative disorders among HTLV-3-infected populations.

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Section: Discussionmentioning

confidence: 95%

Section: Characterization Of the Htlv/stlv-3 Tax Proteinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

et al. 2006

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“…8,10 Other examples are cycD2, Pro-IL16 and CDK4. 11 Tax can also interfere with the cell cycle progression through the transcriptional activation or repression of p18 INK4c , cyc A, cyc C, cyc D 2 , cyc E, CDK2, p21 (CIP1/WAF1) and E2F. 11 Moreover, Tax interferes with the regulation of the cell cycle at the post-translational level by forming a complex with cyclin D3, which induces its phosphorylation.…”

Section: Transcription Factorsmentioning

confidence: 99%

Proapoptotic regimes for HTLV-I-transformed cells: targeting Tax and the NF-κB pathway

Kfoury

Nasr²,

Hermine³

et al. 2005

Cell Death Differ

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Mature T‐cell leukemias

Ravandi

Kantarjian

Jones

et al. 2005

Cancer

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Mature T-cell and NK-cell leukemias are a group of relatively uncommon neoplasms derived from mature or postthymic T-cells accounting for a relatively small percentage of lymphoid malignancies. The recent availability of modern immunophenotypic and molecular tools has allowed a better distinction of these disorders from their B-cell counterparts. Similarly, identification of recurrent cytogenetic abnormalities, as well as plausible mechanisms through which these molecular events influence cellular signaling pathways, have created further insight into the pathogenesis of these disorders. Furthermore, the availability of new agents such as alemtuzumab has generated significant interest in devising specific therapeutic strategies for these malignancies. Herein, we review the clinical and pathological features of mature T-cell leukemias.

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Life, Death, and Tax: Role of HTLV-I Oncoprotein in Genetic Instability and Cellular Transformation

Cited by 160 publications

References 110 publications

The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

The tax protein from the primate T-cell lymphotropic virus type 3 is expressed in vivo and is functionally related to HTLV-1 Tax rather than HTLV-2 Tax

Proapoptotic regimes for HTLV-I-transformed cells: targeting Tax and the NF-κB pathway

Mature T‐cell leukemias

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