Tax ubiquitylation and sumoylation control critical cytoplasmic and nuclear steps of NF-kappaB activation.
The Tax oncoprotein plays a crucial role in the proliferation and transformation of human T-cell leukemia virus type I (HTLV-I)-infected T lymphocytes through various mechanisms, including activation of the nuclear factor (NF)-kappaB pathway. We found that cytoplasmic ubiquitylation of Tax C-terminal lysines is critical for Tax binding to the IkappaB kinase complex and subsequent nuclear translocation of RelA. Conversely, we demonstrate that the same lysines are sumoylated in the nucleus, an event required for the formation of RelA/p300-enriched Tax nuclear bodies and full NF-kappaB transcriptional activation. In contrast, Tax ubiquitylation and sumoylation are dispensable for its activation of cyclic adenosine monophosphate response element binding protein (CREB)-dependent genes. Thus, ubiquitylation and sumoylation of the same residues of Tax regulate 2 essential steps controlling NF-kappaB activation, demonstrating how these posttranslational modifications can cooperate to promote Tax-induced transformation.
Nasr
Rihab
R
Department of Internal Medicine, American University of Beirut, PO Box 113-6044, Beirut, Lebanon.
Chiari
Estelle
E
El-Sabban
Marwan
M
Mahieux
Renaud
R
Kfoury
Youmna
Y
Abdulhay
Maher
M
Yazbeck
Victor
V
Hermine
Olivier
O
de Thé
Hugues
H
Pique
Claudine
C
Bazarbachi
Ali
A
D001665:Binding Sites; D002467:Cell Nucleus / Q000502:physiology*; D003593:Cytoplasm / Q000502:physiology; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D015490:HTLV-I Infections; D006801:Humans; D019169:Jurkat Cells; D008239:Lysine; D016296:Mutagenesis; D016328:NF-kappa B / Q000378:metabolism*; D010957:Plasmids; D015533:Transcriptional Activation; D014178:Translocation, Genetic; D025801:Ubiquitin / Q000378:metabolism*
D016356:Gene Products, tax; D016328:NF-kappa B; D025801:Ubiquitin; D008239:Lysine