Exclusive Ubiquitination And Sumoylation On Overlapping Lysine Residues Mediate Nf-Kappa B Activation By The Human T-Cell Leukemia Virus Tax Oncoprotein

in Molecular and Cellular Biology (2005), 25(23), 10391-406

The transcription factor NF-kappaB is critical for the induction of cancer, including adult T-cell leukemia, which is linked to infection by human T-cell leukemia virus type 1 and the expression of its ... [more ▼]

The transcription factor NF-kappaB is critical for the induction of cancer, including adult T-cell leukemia, which is linked to infection by human T-cell leukemia virus type 1 and the expression of its regulatory protein Tax. Although activation of the NF-kappaB pathway by Tax involves its interaction with the regulatory subunit of the IkappaB kinase (IKK) complex, NEMO/IKKgamma, the mechanism by which Tax activates specific cellular genes in the nucleus remains unknown. Here, we demonstrate that the attachment of SUMO-1 to Tax regulates its localization in nuclear bodies and the recruitment of both the RelA subunit of NF-kappaB and free IKKgamma in these nuclear structures. However, this sumoylation step is not sufficient for the activation of the NF-kappaB pathway by Tax. This activity requires the prior ubiquitination and colocalization of ubiquitinated Tax with IKK complexes in the cytoplasm and the subsequent migration of the RelA subunit of NF-kappaB to the nucleus. Thus, the ubiquitination and sumoylation of Tax function in concert to result in the migration of RelA to the nucleus and its accumulation with IKKgamma in nuclear bodies for activation of gene expression. These modifications may result in targets for the treatment of adult T-cell leukemia. [less ▲]

Overlapping Cre And E Box Motifs In The Enhancer Sequences Of The Bovine Leukemia Virus 5 ' Long Terminal Repeat Are Critical For Basal And Acetylation-Dependent Transcriptional Activity Of The Viral Promoter: Implications For Viral Latency

in Journal of Virology (2004), 78(24),

Reduced Cell Turnover In Bovine Leukemia Virus-Infected, Persistently Lymphocytotic Cattle

in Journal of Virology (2003), 77(24),

Oncoviral Bovine Leukemia Virus G4 And Human T-Cell Leukemia Virus Type 1 P13(Ii) Accessory Proteins Interact With Farnesyl Pyrophosphate Synthetase

in Journal of Virology (2002), 76(3),

Suboptimal Enhancer Sequences Are Required For Efficient Bovine Leukemia Virus Propagation In Vivo: Implications For Viral Latency

in Journal of Virology (2001), 75(15),

Genetic Determinants Of Bovine Leukemia Virus Pathogenesis

in Aids Research and Human Retroviruses (2000), 16(16), 1787-95

The understanding of HTLV-induced disease is hampered by the lack of a suitable animal model allowing the study of both viral replication and leukemogenesis in vivo. Although valuable information has been ... [more ▼]

The understanding of HTLV-induced disease is hampered by the lack of a suitable animal model allowing the study of both viral replication and leukemogenesis in vivo. Although valuable information has been obtained in different species, such as rabbits, mice, rats, and monkeys, none of these systems was able to conciliate topics as different as viral infectivity, propagation within the host, and generation of leukemic cells. An alternate strategy is based on the understanding of diseases induced by viruses closely related to HTLV-1, like bovine leukemia virus (BLV). Both viruses indeed belong to the same subfamily of retroviruses, harbor a similar genomic organization, and infect and transform cells of the hematopoietic system. The main advantage of the BLV system is that it allows direct experimentation in two different species, cattle and sheep. [less ▲]

Long-Term Protection Against Bovine Leukaemia Virus Replication In Cattle And Sheep

in Journal of General Virology (2000), 81

Bovine Leukemia Virus-Induced Persistent Lymphocytosis In Cattle Does Not Correlate With Increased Ex Vivo Survival Of B Lymphocytes

in Journal of Virology (1999), 73(2),

In Vitro And In Vivo Oncogenic Potential Of Bovine Leukemia Virus G4 Protein

in Journal of Virology (1998), 72(3),

Conservative Mutations In The Immunosuppressive Region Of The Bovine Leukemia Virus Transmembrane Protein Affect Fusion But Not Infectivity In Vivo

in Journal of Biological Chemistry (1998), 273(21),