AWARDS FOR THE CPBS’S NADIR MECHTI TEAM.
The article http://www.ncbi.nlm.nih.gov/pubmed/... from the CPBS’s Nadir Mechti team "Interaction hôtes virus et immunité innée" http://www.cpbs.cnrs.fr/spip.php?ru... has been selected as a "Spotlight" by the Journal of Virology and rewieved for "Priority Evaluation" by Future Virology : http://www.ncbi.nlm.nih.gov/pubmed?...
Summary
This study examines downstream signaling events of PI3K/AKT in the context of human T cell leukemia virus type 1 (HTLV-1) infection. The authors have demonstrated that the HTLV-1 Tax oncoprotein triggers the ubiquitination and proteasomal degradation of the FoxO4 transcription factor. Phosphorylation by AKT is requisite for Tax-induced FoxO4 degradation since mutation of the AKT phosphorylation sites abrogates FoxO4 degradation. Furthermore, Tax enhances the interaction between FoxO4 and the E3 ubiquitin ligase MDM2 which presumably leads to FoxO4 ubiquitination. Consistently, knockdown of MDM2 with a shRNA plasmid attenuates FoxO4 ubiquitination, revealing an important role for MDM2 in Tax-induced FoxO4 ubiquitination. Finally, Tax represses FoxO4 transcriptional activity in a dose-dependent manner. Taken together, these findings suggest that Tax inactivates the tumor suppressor FoxO4 downstream of PI3K/AKT, which may play a role in HTLV-1-induced oncogenesis.