Human T-lymphotropic virus proteins and post-translational modification pathways

Figure 3 Diagram representing Tax localization and function controlled by protein post-translational modifications. After translation, Tax could be phosphorylated at Ser-160 and hence stabilized by Pin1, preventing its poly-ubiquitination with subsequent lysosomal degradation (top right). Tax is K-63 poly-ubiquitinated by Ubc13, promoting its relocation to a region between endoplasmic reticulum (ER) and cis-Golgi, where it interacts with I-κB kinase (IKK)γ, the overexpressed Tab2 and RelA. UPS20 can de-ubiquitinate Tax (centre). From cis-Golgi, Tax shuttles to MTOC, where it interacts with IKKγ, RanBP1 and Ran. From MTOC, Tax shuttles to Tax-related nuclear bodies containing Sc-35 and RNAPolII. There, it is acetylated by p300 and SUMOylated, probably by Ubc9 (left). In nuclear bodies, Tax interacts with p300, IKKγ, RelA and the methyltransferase SUV39H1. Furthermore, Tax interacts also with phosphorylated cyclic AMP response element binding protein (CREB). PDLIM2 has proven to cause K48 poly-ubiquitination of Tax, promoting its nuclear proteosomal degradation after translocation from nuclear bodies and MTOC (bottom left). Tax displays its nuclear functions when Ser-300 or Ser-301 are phosphorylated (nucleus). After UV treatment, mono-ubiquitinated Tax is exported to the cytoplasm through CRM1 (top). Thin arrows represent relocation or modification; P: Phosphorylation; S: SUMO1; A: Acetylation; Ub: Ubiquitin; K48 or K63: Chains of ubiquitin; UV: Ultraviolet light exposure; protein overexpression in infected cells is represented by thick arrows.