25 November 2020
HTLV-1: The shuttling pathways of the tax protein
Published online 17 November 2010
Tax is a protein encoded by the Human T-lymphotropic virus Type I (HTLV-1) and plays a pivotal role in how the virus activates the NF-κB pathway, which regulates inflammation and oncogenesis, to trigger adult T-cell leukemia/lymphoma (ATL).
A team of researchers from the American University in Beirut, Lebanon, worked with a French team to study the movement of Tax within the cell to understand how it works.
They found that tax shuttles between nuclear bodies within the cell and but also moves from these nuclear bodies to the centrosome and back. The trip depends on its post-translational modifications. When tax is bound to K63 ubiquitin it moves to the centrosome and to certain nuclear bodies rich in small ubiquitin-like modifier (SUMO). In addition to their role in transcription, these nuclear bodies were shown to be active sites of sumoylation.
After it arrives at these nuclear bodies, tax is sumolated, which sends it to the centrosome where it triggers the NF-κB pathway. Finally, further ubiquitylation of the protein with K48 ubiquitin moves it to the nucleoplasm where it undergoes proteasomal degradation.
The researchers suggest that this shuttling of tax between the nuclear bodies and the centrosome, controlled by these small post-translational modifications, increases the efficiency of the relatively small HTLV-1 genome.
- Kfoury, Y. et al. Tax ubiquitylation and SUMOylation control the dynamic shuttling of Tax and NEMO between Ubc9 nuclear bodies and the centrosome. Blood. 19 October, 2010. 10.1182/blood-2010-05-285742