title: Tax ubiquitylation and sumoylation control critical cytoplasmic and nuclear steps of NF-kappaB activation.
abstract: 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.
authors.affiliation: Department of Internal Medicine, American University of Beirut, PO Box 113-6044, Beirut, Lebanon.
authors.forename: Rihab
authors.initials: R
authors.lastname: Nasr
authors.forename: Estelle
authors.initials: E
authors.lastname: Chiari
authors.forename: Marwan
authors.initials: M
authors.lastname: El-Sabban
authors.forename: Renaud
authors.initials: R
authors.lastname: Mahieux
authors.forename: Youmna
authors.initials: Y
authors.lastname: Kfoury
authors.forename: Maher
authors.initials: M
authors.lastname: Abdulhay
authors.forename: Victor
authors.initials: V
authors.lastname: Yazbeck
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Hugues
authors.initials: H
authors.lastname: de Thé
authors.forename: Claudine
authors.initials: C
authors.lastname: Pique
authors.forename: Ali
authors.initials: A
authors.lastname: Bazarbachi
mesh_terms: 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*
chemical_list: D016356:Gene Products, tax; D016328:NF-kappa B; D025801:Ubiquitin; D008239:Lysine