- Poster presentation
- Open Access
TRAF5-mediated Tax ubiquitination modulates IKK phosphorylation but not binding to NEMO
© Bonnet et al; licensee BioMed Central Ltd. 2014
- Published: 7 January 2014
- Epstein Barr Virus
- Ubiquitin Ligase
- Catalytic Subunit
- Powerful Activator
- Regulatory Subunit
Tax is a powerful activator of the NF-kB pathway, a property shown to be required for HTLV-1-induced immortalization of primary T lymphocytes. A pivotal step in the stimulation of this pathway is the activation of the cytoplasmic IkB-kinase (IKK) complex, which consists of two catalytic subunits, IKK-alpha and beta and a regulatory subunit, IKK-gamma/NEMO. Previous studies showed that the ability of Tax to bind to and activate the IKK complex depends on its prior conjugation to ubiquitin. TRAF5, a member of the TNF Receptor-Associated Factor family, is an adaptor protein and E3 ubiquitin ligase which functions downstream various membrane receptors, notably for the activation of the NF-kB pathway. Interestingly, TRAF5 was also shown to interact with the Epstein Barr Virus (EBV)-encoded LMP1 oncoprotein and to contribute to LMP1-induced IKK activation. In this study, we investigated whether TRAF5 could also be a functional partner of Tax. We found that overexpressing TRAF5 significantly increases endogenous Tax ubiquitination while conversely endogenous Tax ubiquitination is reduced upon siRNA-mediated TRAF5 silencing. Surprisingly, preventing TRAF5-mediated Tax ubiquitination by siRNA depletion of TRAF5 does not affect Tax binding to endogenous NEMO. However, Tax-induced phosphorylation of IKK-alpha/beta is significantly decreased in the same setting, which coincided with a decreased ability of Tax to activate a NF-kB promoter. These findings reveal that TRAF5 mediates Tax ubiquitination for IKK activation and suggest that Tax binding to NEMO and Tax-induced IKK phosphorylation are regulated by distinct molecular determinants.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.