Localization of human T-cell lymphotropic virus type II Tax protein is dependent upon a nuclear localization determinant in the N-terminal region

Turci, Marco; Lorenzi, Pamela; Righi, Paola; Bertazzoni, Umberto

doi:10.1016/j.gene.2005.09.043

Cited by 27 publications

(28 citation statements)

References 32 publications

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“…Alternatively, distinct Tax1 versus Tax2 posttranslational modification patterns could be a consequence of distinct subcellular localizations that could be critical for interaction with the modification machineries. Indeed, as mentioned above, Tax1 is both nuclear and cytoplasmic while Tax2 is predominantly cytoplasmic (25,26,28).…”

Section: Resultsmentioning

confidence: 72%

“…Tax1 forms nuclear speckles (16)(17)(18)(19)(20) and is detected in Golgi/centrosome-associated cytoplasmic domains (21)(22)(23)(24). Although it is also detectable in the nucleus, Tax2 is predominantly found in the cytoplasm of the cells (25)(26)(27)(28) (for a review, see reference 29). Both proteins possess a nuclear export sequence located between amino acids (aa) 188 and 202 (30,31).…”

mentioning

confidence: 99%

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Human T Cell Leukemia Virus Type 2 Tax-Mediated NF-κB Activation Involves a Mechanism Independent of Tax Conjugation to Ubiquitin and SUMO

Journo

Bonnet

Favre-Bonvin

et al. 2013

J Virol

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f Permanent activation of the NF-B pathway by the human T cell leukemia virus type 1 (HTLV-1) Tax (Tax1) viral transactivator is a key event in the process of HTLV-1-induced T lymphocyte immortalization and leukemogenesis. Although encoding a Tax transactivator (Tax2) that activates the canonical NF-B pathway, HTLV-2 does not cause leukemia. These distinct pathological outcomes might be related, at least in part, to distinct NF-B activation mechanisms. Tax1 has been shown to be both ubiquitinated and SUMOylated, and these two modifications were originally proposed to be required for Tax1-mediated NF-B activation. Tax1 ubiquitination allows recruitment of the IKK-␥/NEMO regulatory subunit of the IKK complex together with Tax1 into centrosome/Golgi-associated cytoplasmic structures, followed by activation of the IKK complex and RelA/p65 nuclear translocation. Herein, we compared the ubiquitination, SUMOylation, and acetylation patterns of Tax2 and Tax1. We show that, in contrast to Tax1, Tax2 conjugation to endogenous ubiquitin and SUMO is barely detectable while both proteins are acetylated. Importantly, Tax2 is neither polyubiquitinated on lysine residues nor ubiquitinated on its N-terminal residue. Consistent with these observations, Tax2 conjugation to ubiquitin and Tax2-mediated NF-B activation is not affected by overexpression of the E2 conjugating enzyme Ubc13. We further demonstrate that a nonubiquitinable, non-SUMOylable, and nonacetylable Tax2 mutant retains a significant ability to activate transcription from a NF-B-dependent promoter after partial activation of the IKK complex and induction of RelA/p65 nuclear translocation. Finally, we also show that Tax2 does not interact with TRAF6, a protein that was shown to positively regulate Tax1-mediated activation of the NF-B pathway.

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Section: Resultsmentioning

confidence: 72%

mentioning

confidence: 99%

Human T Cell Leukemia Virus Type 2 Tax-Mediated NF-κB Activation Involves a Mechanism Independent of Tax Conjugation to Ubiquitin and SUMO

Journo

Bonnet

Favre-Bonvin

et al. 2013

J Virol

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“…The N-terminal region of Tax-1 protein contains a CREB-binding region, a zinc-finger domain, and binding domains required for interaction with proteasomal subunits, transcriptional coactivators, and proteins involved in transcription, cell cycle progression, and in cell signaling regulations [1]. The first 60 aa of Tax-1 also contains a nuclear localization signal (NLS) [33,34], whereas we have mapped a nuclear localization determinant (NLD) in the first 42 aa of Tax-2 [35]. Furthermore, in Tax-2, an additional localization domain of about 10 aa at position 89–113 has been demonstrated to be responsible for the divergent cellular localization as compared to Tax-1 [36].…”

Section: Protein Structurementioning

confidence: 99%

“…Tax-2 intracellular localization has been studied by several authors and it was initially reported to be predominantly localized in the cytoplasm [30,35,36,51,113] with no clear evidence of localization within the nuclear bodies. However, using novel systems to compare concomitantly Tax-1 and Tax-2, we have demonstrated that Tax-2B is also present in nuclear bodies [72].…”

Section: Cellular Localization Of Tax Proteinsmentioning

confidence: 99%

Intracellular Localization and Cellular Factors Interaction of HTLV-1 and HTLV-2 Tax Proteins: Similarities and Functional Differences

Bertazzoni

Turci

Avesani

et al. 2011

Viruses

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Human T-lymphotropic viruses type 1 (HTLV-1) and type 2 (HTLV-2) present very similar genomic structures but HTLV-1 is more pathogenic than HTLV-2. Is this difference due to their transactivating Tax proteins, Tax-1 and Tax-2, which are responsible for viral and cellular gene activation? Do Tax-1 and Tax-2 differ in their cellular localization and in their interaction pattern with cellular factors? In this review, we summarize Tax-1 and Tax-2 structural and phenotypic properties, their interaction with factors involved in signal transduction and their localization-related behavior within the cell. Special attention will be given to the distinctions between Tax-1 and Tax-2 that likely play an important role in their transactivation activity.

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“…The leucine zipper regions present in the central region of Tax-1 are responsible for activation of the non-canonical NF-κB pathway (Higuchi and Fujii, 2009). The nuclear localization and nuclear export signals of Tax-1 and Tax-2 present significant differences which could explain the predominant nuclear localization of Tax-1 compared to Tax-2 (Turci et al, 2006, 2009; Avesani et al, 2010). …”

Section: Tax Proteins and Their Interactions With Cellular Pathwaysmentioning

confidence: 98%

HTLV-1 and HTLV-2: highly similar viruses with distinct oncogenic properties

et al. 2014

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HTLV-1 and HTLV-2 share broad similarities in their overall genetic organization and expression pattern, but they differ substantially in their pathogenic properties. This review outlines distinctive features of HTLV-1 and HTLV-2 that might provide clues to explain their distinct clinical outcomes. Differences in the kinetics of viral mRNA expression, functional properties of the regulatory and accessory proteins, and interactions with cellular factors and signal transduction pathways are discussed.

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Localization of human T-cell lymphotropic virus type II Tax protein is dependent upon a nuclear localization determinant in the N-terminal region

Cited by 27 publications

References 32 publications

Human T Cell Leukemia Virus Type 2 Tax-Mediated NF-κB Activation Involves a Mechanism Independent of Tax Conjugation to Ubiquitin and SUMO

Human T Cell Leukemia Virus Type 2 Tax-Mediated NF-κB Activation Involves a Mechanism Independent of Tax Conjugation to Ubiquitin and SUMO

Intracellular Localization and Cellular Factors Interaction of HTLV-1 and HTLV-2 Tax Proteins: Similarities and Functional Differences

HTLV-1 and HTLV-2: highly similar viruses with distinct oncogenic properties

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