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

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

Critical role of hnRNP A1 in HTLV-1 replication in human transformed T lymphocytes

BACKGROUND: In this study, we have examined the role of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) in viral gene expression in T lymphocytes transformed by HTLV-1. RESULTS: We have previously observed that hnRNP A1 (A1) down-modulates the post transcriptional activity of Rex protein of HTLV-1. Here, we tested whether the ectopic expression of a dominant negative mutant (NLS-A1-HA) defective in shuttling activity or knockdown of the hnRNPA1 gene using RNA interference could inhibit Rex-mediated export of viral mRNAs in HTLV-1 producing C91PL T-cells. We show that the expression of NLS-A1-HA does not modify the export of Rex-dependent viral mRNAs. Conversely, inhibiting A1 expression in C91PL cells by RNA interference provoked an increase in the Rex-dependent export of unspliced and singly spliced mRNAs. Surprisingly, we also observed a significant increase in proviral transcription and an accumulation of unspliced mRNAs, suggesting that the splicing process was affected. Finally, A1 knockdown in C91PL cells increased viral production by these cells. Thus, hnRNP A1 is implicated in the modulation of the level of HTLV-1 gene expression in T cells transformed by this human retrovirus. CONCLUSIONS: These observations provide an insight into a new cellular control of HTLV-1 replication and suggest that hnRNP A1 is likely part of the regulatory mechanisms of the life cycle of this human retrovirus in T cells

Cytoplasmic and nuclear events controlling Tax-mediated activation of the NF-κB pathway: involvement of TAB2, IKKgamma/NEMO and calreticulin

The Tax oncoprotein of HTLV-1 initiates T-cell transformationby dysregulating cell cycle progression andinhibiting DNA damage responses. The subsequentgenomic instability might result in constitutive activationof the NF-B pathway observed in HTLV-1-transformedT lymphocytes. Our previous results indicatedthat differential modifications of Tax by ubiquitinationor sumoylation controlled its retention either in thecytoplasm or in the nucleus, respectively. Here we showthat Tax is targeted to pre-existing punctate cytoplasmicstructures which contain the TNF-receptor associatedprotein 2 (TAB2)

Comparative analysis of HTLV-1 and HTLV-2 post-translational modifications of Tax proteins in relation to their intracellular localization and activation of gene expression

Poster presentatio

STAT5 Is an Ambivalent Regulator of Neutrophil Homeostasis

BACKGROUND: Although STAT5 promotes survival of hematopoietic progenitors, STAT5-/- mice develop mild neutrophilia. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that in STAT5-/- mice, liver endothelial cells (LECs) autonomously secrete high amounts of G-CSF, allowing myeloid progenitors to overcompensate for their intrinsic survival defect. However, when injected with pro-inflammatory cytokines, mutant mice cannot further increase neutrophil production, display a severe deficiency in peripheral neutrophil survival, and are therefore unable to maintain neutrophil homeostasis. In wild-type mice, inflammatory stimulation induces rapid STAT5 degradation in LECs, G-CSF production by LECs and other cell types, and then sustained mobilization and expansion of long-lived neutrophils. CONCLUSION: We conclude that STAT5 is an ambivalent factor. In cells of the granulocytic lineage, it exerts an antiapoptotic function that is required for maintenance of neutrophil homeostasis, especially during the inflammatory response. In LECs, STAT5 negatively regulates granulopoiesis by directly or indirectly repressing G-CSF expression. Removal of this STAT5-imposed brake contributes to induction of emergency granulopoiesis.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Utilisation de mutants à déficience respiratoire thermosensible pour l'étude de la biogenèse des mitochondries chez la levure

Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe

Modifications de la cytochrome oxydase particulaire chez un mutant thermosensible de levure

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Regulation of gene expression by HTLV-I tax protein

The human T-cell leukemia virus type I or HTLV-I is the causative agent of adult T-cell leukemia. A protein encoded by HTLV-I, Tax, activates viral gene expression and is essential for transforming T-lymphocytes. Tax activates HTLV-I gene expression via interactions with the ATF/CREB proteins and the coactivators CBP/p300 which assemble as a multiprotein complex on regulatory elements known as 21-bp repeats in the HTLV-I LTR. Tax can also activate expression from cellular genes including the interleukin-2 (IL-2) and the L-2 receptor genes via increases in nuclear levels of NF-κB. Tax modulation of gene expression via the ATF/CREB and NF-κB pathways is linked to its transforming properties. This review discusses the mechanisms by which tax regulates viral and cellular gene expression.SCOPUS: ar.jinfo:eu-repo/semantics/publishe