Acetylation of the human T-cell leukemia virus type 1 Tax oncoprotein by p300 promotes activation of the NF-κB pathway

Lodewick, Julie; Lamsoul, Isabelle; Perucatti, A.; Lebrun, Sylvie; Burny, Arsène; Ratner, Lee; Bex, Françoise

doi:10.1016/j.virol.2008.12.043

Cited by 46 publications

(63 citation statements)

References 67 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lodewick et al recently showed that both Tax1 and Tax2 are acetylated (65). Since acetylation occurs on lysine residues, it is expected that Tax2-K0 would be defective for acetylation, which might in turn impact its transcriptional activity.…”

Section: Resultsmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

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

View full text Add to dashboard Cite

show abstract

“…Ubiquitination, sumoylation, acetylation, and phosphorylation of Tax have been shown to influence its transcriptional function (5,9,22,23,25,28,34,35,40). Tax ubiquitination has been reported to be required for its activation of NF-B, and it has been found that the Tax-polyubiquitin chains are predominantly K63 linked (40).…”

Section: Resultsmentioning

confidence: 99%

Ubiquitin-Specific Peptidase 20 Targets TRAF6 and Human T Cell Leukemia Virus Type 1 Tax To Negatively Regulate NF-κB Signaling

Yasunaga

Lin

et al. 2011

J Virol

View full text Add to dashboard Cite

“…10,11 Posttranslational modification of proteins regulates protein functions by modifying their subcellular localization, stability, and/or network of interaction. We and others have described different forms of Tax posttranslational modifications including phosphorylation, 12,13 acetylation, 14 ubiquitylation, and small ubiquitin-like modifier (SUMO)ylation, 15,16 all of which are implicated in Tax-mediated activation of gene expression. Indeed, we showed that Tax is differentially ubiquitylated by either K-48 ubiquitin chains leading to Tax degradation by the proteasome or by K-63 ubiquitin chains that mediates IKK recruitment to the centrosome and IKK activation.…”

Section: Introductionmentioning

confidence: 99%

Tax ubiquitylation and SUMOylation control the dynamic shuttling of Tax and NEMO between Ubc9 nuclear bodies and the centrosome

Kfoury

Setterblad

El-Sabban

et al. 2011

Blood

View full text Add to dashboard Cite

The human T-lymphotropic virus type I oncoprotein Tax is critical for T-cell transformation, acting mainly through nuclear factor kappa B essential modulator (NEMO) binding and subsequent nuclear factor-B activation. Tax localizes to Tax nuclear bodies and to the centrosome and is subjected to ubiquitylation and small ubiquitin-like modifier (SUMO)ylation, which are both necessary for complete transcriptional activation. Using the photoconvertible fluorophore Dendra-2 coupled with live video confocal microscopy, we show for the first time that the same Tax molecule shuttles among Tax nuclear bodies and between these nuclear bodies and the centrosome, depending on its posttranslational modifications. Ubiquitylation targets Tax to nuclear bodies to which NEMO is recruited and subsequently SUMOylated. We also demonstrate that Tax nuclear bodies contain the SUMOylation machinery including SUMO and the SUMO conjugating enzyme Ubc9, strongly suggesting that these nuclear bodies represent sites of active SUMOylation. IntroductionTax, the viral oncoprotein encoded by the pX region of the human T-lymphotropic virus type I (HTLV-I) genome is a key player in the pathogenesis of HTLV-I-associated diseases, mainly adult T-cell leukemia/lymphoma and tropical spastic paraparesis/HTLVassociated myelopathy. Tax deregulates the cellular machinery at multiple levels leading to the transformation of HTLV-I-infected T lymphocytes, predominantly through the activation of the nuclear factor-B (NF-B) pathway, which regulates key genes implicated in inflammation, apoptosis, and oncogenesis. 1,2 A corner stone in this NF-B activation is Tax binding to the regulatory subunit of the IB kinase (IKK) complex, IKK␥ (also known as NEMO). 3,4 Tax binding to NEMO phosphorylates both IKK␣ and IKK␤ leading to the formation of the IKK complex that phosphorylates the NF-B inhibitors IBs. This leads to the nuclear translocation of the active NF-B dimers and to transcriptional activation of target genes. 5 Tax/NEMO binding can also induce the IKK␣-dependent processing of the NF-B p100 precursor protein to its active p52 form. 6 Tax displays a dual nuclear and cytoplasmic localization with functions that are essential for cellular transformation in each compartment. 7,8 In the nucleus, Tax is predominantly located in RelA-enriched nuclear bodies. 9 In the cytoplasm, a major fraction of Tax lays in perinuclear hotspots colocalizing with the centrosome or microtubule organizing center in close association with the cis-Golgi compartment. 10,11 Posttranslational modification of proteins regulates protein functions by modifying their subcellular localization, stability, and/or network of interaction. We and others have described different forms of Tax posttranslational modifications including phosphorylation, 12,13 acetylation, 14 ubiquitylation, and small ubiquitin-like modifier (SUMO)ylation, 15,16 all of which are implicated in Tax-mediated activation of gene expression. Indeed, we showed that Tax is differentially ubiquitylated by either K-48 ubiquitin...

show abstract

Acetylation of the human T-cell leukemia virus type 1 Tax oncoprotein by p300 promotes activation of the NF-κB pathway

Cited by 46 publications

References 67 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

Ubiquitin-Specific Peptidase 20 Targets TRAF6 and Human T Cell Leukemia Virus Type 1 Tax To Negatively Regulate NF-κB Signaling

Tax ubiquitylation and SUMOylation control the dynamic shuttling of Tax and NEMO between Ubc9 nuclear bodies and the centrosome

Contact Info

Product

Resources

About