HTLV-2B Tax oncoprotein is modified by ubiquitination and sumoylation and displays intracellular localization similar to its homologue HTLV-1 Tax

Turci, Marco; Lodewick, Julie; Righi, Paola; Perucatti, A.; Bex, Françoise; Bertazzoni, Umberto

doi:10.1016/j.virol.2009.01.003

Cited by 28 publications

(42 citation statements)

References 22 publications

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“…Consistent with previous studies, Tax localization was heterogeneous with staining in both the cytoplasm and nucleus in 293T cells (Fig. 3A) (48). However, upon siRNA-induced silencing of STAMBPL1, a strongly nuclear distribution of Tax in the Tax speckled structure (TSS) was readily apparent (Fig.…”

Section: Stambpl1 Is a Positive Regulator Of Tax-mediated Nf-b Signalsupporting

confidence: 91%

“…Wade Harper and obtained from Addgene (plasmid 22559) (45). Flag-Tax1 was a gift from U. Bertazzoni (48). The following antibodies were used in this study: anti-STAMBPL1 (ab99172; Abcam), anti-p100/ p52 (Santa Cruz Biotechnology), anti-␤-actin (AC15; Abcam), anti-IB␣ (C-21; Santa Cruz Biotechnology), anti-phospho-IB␣ (14D4; Cell Signaling), and anti-TATA-binding protein (anti-TATA-BP) (MAB3658; Millipore).…”

Section: Methodsmentioning

confidence: 99%

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An RNA Interference Screen Identifies the Deubiquitinase STAMBPL1 as a Critical Regulator of Human T-Cell Leukemia Virus Type 1 Tax Nuclear Export and NF-κB Activation

Lavorgna

Harhaj

2012

J Virol

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The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein actively shuttles between the nucleus, where it interacts with transcriptional and splicing regulatory proteins, and the cytoplasm, where it activates NF-κB. Posttranslational modifications of Tax such as ubiquitination regulate its subcellular localization and hence its function; however, the regulation of Tax trafficking and NF-κB activation by host factors is poorly understood. By screening a deubiquitinating (DUB) enzyme small interfering RNA (siRNA) library, we identified the metalloprotease STAM-binding protein-like 1 (STAMBPL1) as a positive regulator of Tax-mediated NF-κB activation. Overexpression of wild-type STAMBPL1, but not a catalytically inactive mutant, enhanced Tax-mediated NF-κB activation, whereas silencing of STAMBPL1 with siRNA impaired Tax activation of both the canonical and noncanonical NF-κB signaling pathways. STAMBPL1 regulated Tax-induced NF-κB signaling indirectly by controlling Tax nuclear/cytoplasmic transport and was required for DNA damage-induced Tax nuclear export. Together, these results reveal that the deubiquitinase STAMBPL1 is a key regulator of Tax trafficking and function.

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Section: Stambpl1 Is a Positive Regulator Of Tax-mediated Nf-b Signalsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

An RNA Interference Screen Identifies the Deubiquitinase STAMBPL1 as a Critical Regulator of Human T-Cell Leukemia Virus Type 1 Tax Nuclear Export and NF-κB Activation

Lavorgna

Harhaj

2012

J Virol

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“…A previous report suggested that, as Tax1, Tax2 was both ubiquitinated and SUMOylated (27). However, in this report, analyses of Tax1 and Tax2 modifications were performed in cells overexpressing ubiquitin or SUMO proteins, which may lead to false-positive results (60).…”

mentioning

confidence: 86%

“…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%

“…Depending on the nature of the inducing signal, NF-B may become activated either through the canonical or the noncanonical pathway. In contrast to Tax2, which activates only the canonical pathway, Tax1 constitutively activates both pathways (25,27,(36)(37)(38)(39)(40)(41). The molecular determinant of the ability to activate the noncanonical pathway has been mapped to Tax1 aa 225 to 232 (41).…”

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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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SUMOylation in Viral Replication and Antiviral Defense

Fan

Zhang

et al. 2022

Advanced Science

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SUMOylation is a ubiquitination-like post-translational modification that plays an essential role in the regulation of protein function. Recent studies have shown that proteins from both RNA and DNA virus families can be modified by SUMO conjugation, which facilitates viral replication. Viruses can manipulate the entire process of SUMOylation through interplay with the SUMO pathway. By contrast, SUMOylation can eliminate viral infection by regulating host antiviral immune components. A deeper understanding of how SUMOylation regulates viral proteins and cellular antiviral components is necessary for the development of effective antiviral therapies. In the present review, the regulatory mechanism of SUMOylation in viral replication and infection and the antiviral immune response, and the consequences of this regulation for viral replication and engagement with antiviral innate immunity are summarized. The potential therapeutic applications of SUMOylation in diseases caused by viruses are also discussed.

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HTLV-2B Tax oncoprotein is modified by ubiquitination and sumoylation and displays intracellular localization similar to its homologue HTLV-1 Tax

Cited by 28 publications

References 22 publications

An RNA Interference Screen Identifies the Deubiquitinase STAMBPL1 as a Critical Regulator of Human T-Cell Leukemia Virus Type 1 Tax Nuclear Export and NF-κB Activation

An RNA Interference Screen Identifies the Deubiquitinase STAMBPL1 as a Critical Regulator of Human T-Cell Leukemia Virus Type 1 Tax Nuclear Export and NF-κB Activation

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

SUMOylation in Viral Replication and Antiviral Defense

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