Regulation of the human T-cell leukemia virus gene expression depends on the localization of regulatory proteins Tax, Rex and p30II in specific nuclear subdomains

Baydoun, Hicham H.; Duc-Dodon, Madeleine; Lebrun, Sylvie; Gazzolo, Louis; Bex, Françoise

doi:10.1016/j.gene.2006.09.008

Cited by 18 publications

(24 citation statements)

References 51 publications

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“…1). We confirmed the appropriate nuclear localization of p30 in this cell type (21,39,40, and data not shown). TLR4 expression on the cell surface of transduced cells was analyzed by flow cytometry with or without stimulation with phorbol myristyl acetate (PMA).…”

Section: Resultssupporting

confidence: 84%

Human T-Cell Leukemia/Lymphoma Virus Type 1 p30, but Not p12/p8, Counteracts Toll-Like Receptor 3 (TLR3) and TLR4 Signaling in Human Monocytes and Dendritic Cells

Fenizia

Fiocchi

Jones

et al. 2014

J Virol

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Section: Resultssupporting

confidence: 84%

Human T-Cell Leukemia/Lymphoma Virus Type 1 p30, but Not p12/p8, Counteracts Toll-Like Receptor 3 (TLR3) and TLR4 Signaling in Human Monocytes and Dendritic Cells

Fenizia

Fiocchi

Jones

et al. 2014

J Virol

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“…Tax recruits a plethora of transcription factors within speckled structures to activate transcription while DNA accumulates at the surface of TSS. 47 We now show that these structures are enriched in phosphorylated forms of MCM2 and in close vicinity to the active …”

mentioning

confidence: 64%

Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program

Boxus

Twizere

Legros

et al. 2012

Blood

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The Tax oncoprotein encoded by the human T-cell leukemia virus type 1 plays a pivotal role in viral persistence and pathogenesis. Human T-cell leukemia virus type 1-infected cells proliferate faster than normal lymphocytes, expand through mitotic division, and accumulate genomic lesions. Here, we show that Tax associates with the minichromosome maintenance MCM2-7 helicase complex and localizes to origins of replication. Tax IntroductionHuman T-cell leukemia virus-1 (HTLV-1) is a retrovirus that infects approximately 20 million people worldwide. 1 Although the majority of infected people remain lifelong asymptomatic carriers, 2% to 5% develop either adult T-cell leukemia (ATL) or chronic inflammatory diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis. 1 Two major hallmarks of HTLV-1-infected cells are: preferential proliferation compared with normal lymphocytes 2 and tendency to accumulate genomic lesions, a prerequisite for oncogenesis. 3,4 Although the molecular mechanisms underlying T-cell transformation remain to be elucidated, it is generally accepted that the virally encoded Tax protein plays a central role. Tax indeed displays pleiotropic activities that cooperate to drive cell cycle progression and perturb genome stability. 4,5 For example, Tax shortens G 1 phase and accelerates transition into S phase by manipulating positive and negative G 1 phase regulators (ie, cyclin D/CDK complex, Rb and CDK inhibitors). [6][7][8] In addition, Tax is thought to indirectly generate DNA damage by suppressing DNA repair processes and competing with cellular DNA damage response (DDR). 4,5 Recent data also support a direct role for Tax-induced reactive oxygen species in the occurrence of DNA lesions. 9 Conceptually, Tax activities are achieved through proteinprotein interactions in both nuclear and cytoplasmic cellular compartments. 10 In the nucleus, Tax accumulates within foci called Tax speckled structures (TSS), 11 which overlap with the cellular machinery required for transcription, splicing, post-transcriptional modifications of proteins, DNA repair, and checkpoint control. 12 In this report, we further demonstrate that Tax recruits the MCM2-7 replicative helicase within the TSS and modulates the program of replication origin firing. Notably, this mechanism favors cell cycle progression and directly compromises genome stability. Methods Plasmids, antibodies, yeast 2-hybrid, and GST pulldownSee supplemental Methods (available on the Blood Web site; see the Supplemental Materials link at the top of the online article). Cell cultureHeLa, Rat-1, and 293GP2 cells were cultured in Dulbecco modified Eagle medium supplemented with 10% FBS and 2mM l-glutamine and penicillin/ streptomycin. Jurkat, HUT78 and JPX9 (Jurkat cell lines stably transfected either with tax-1 gene driven by a metallothionein-inducible promoter) were kept in RPMI 1640 supplemented with 10% FBS, 2mM l-glutamine, and penicillin/streptomycin. Expression of the viral protein was induced in JPX9 cells by adding 120 M zinc chloride...

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“…These foci, first observed by immunofluorescence staining and confocal microscopy, were then characterized by thin section electron microscopy and immunogold labeling [34,70], revealing that the Tax foci were not aggregates, but prominent nuclear bodies. Unique spherical structures of 2 to 4 μm in diameter with a well-defined architecture of electron dense 20 nm granules aligned along fibers was observed in Tax expressing cells (Figure 3A).…”

Section: Distribution Of Tax In the Nucleusmentioning

confidence: 99%

“…The Tax NBs are localized in the interchromatin space and tightly associated with the nuclear matrix. Contacts with loops of decondensed chromatin occur at the surface, but DNA is not present in the core of the structure (Figure 3A, Chr), as evidenced by using a highly sensitive technique for the detection of DNA by electron microscopy [70]. …”

Section: Distribution Of Tax In the Nucleusmentioning

confidence: 99%

Move or Die: the Fate of the Tax Oncoprotein of HTLV-1

Lodewick

Lamsoul

Bex

2011

Viruses

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The HTLV-1 Tax protein both activates viral replication and is involved in HTLV-1-mediated transformation of T lymphocytes. The transforming properties of Tax include altering the expression of select cellular genes via activation of cellular pathways and perturbation of both cell cycle control mechanisms and apoptotic signals. The recent discovery that Tax undergoes a hierarchical sequence of posttranslational modifications that control its intracellular localization provides provocative insights into the mechanisms regulating Tax transcriptional and transforming activities.

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Regulation of the human T-cell leukemia virus gene expression depends on the localization of regulatory proteins Tax, Rex and p30II in specific nuclear subdomains

Cited by 18 publications

References 51 publications

Human T-Cell Leukemia/Lymphoma Virus Type 1 p30, but Not p12/p8, Counteracts Toll-Like Receptor 3 (TLR3) and TLR4 Signaling in Human Monocytes and Dendritic Cells

Human T-Cell Leukemia/Lymphoma Virus Type 1 p30, but Not p12/p8, Counteracts Toll-Like Receptor 3 (TLR3) and TLR4 Signaling in Human Monocytes and Dendritic Cells

Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program

Move or Die: the Fate of the Tax Oncoprotein of HTLV-1

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