Tax ubiquitylation and SUMOylation control the dynamic shuttling of Tax and NEMO between Ubc9 nuclear bodies and the centrosome.
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-κB 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. Finally, both ubiquitylation and SUMOylation of Tax control NEMO targeting to the centrosome. Altogether, we are proposing a model where both ubiquitylation and SUMOylation of Tax control the shuttling of Tax and NEMO between the cytoplasmic and nuclear compartments.
Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.
Youmna
Y
Kfoury
Niclas
N
Setterblad
Marwan
M
El-Sabban
Alessia
A
Zamborlini
Zeina
Z
Dassouki
Hiba
H
El Hajj
Olivier
O
Hermine
Claudine
C
Pique
Hugues
H
de Thé
Ali
A
Saïb
Ali
A
Bazarbachi
D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D018385:Centrosome / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D016356:Gene Products, tax / Q000502:physiology*; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D058207:Sumoylation; D015533:Transcriptional Activation; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D016356:Gene Products, tax; C491731:IKBKG protein, human; D016328:NF-kappa B; D012333:RNA, Messenger; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; D051550:I-kappa B Kinase; D000098843:Ubiquitin-Conjugating Enzyme UBC9