Skip to main content
. 2020 Jul 7;9(7):543. doi: 10.3390/pathogens9070543

Figure 1.

Figure 1

Tax activation of canonical and noncanonical NF-κB signaling. Tax interacts with ring finger protein 8 (RNF8) and linear ubiquitin assembly complex (LUBAC) to recruit K63-linked polyubiquitin chains and linear ubiquitin chains, respectively, to induce IκB kinase (IKK) activation. Tax also interacts with IκBα and p105 to disrupt NF-κB/IκB complexes with subsequent phosphorylation and proteasomal degradation of IκBα and processing to p50, respectively. Tax interacts with and promotes the nuclear translocation of active NF-κB dimers to enhance DNA binding and transcriptional activity. Tax also activates noncanonical NF-κB signaling through interaction with IκB kinase α (IKKα) and NF-κB essential modulator (NEMO) to induce the proteasomal processing of p100 to active p52 and trigger its nuclear translocation along with RelB to activate NF-κB target genes. Tax also interacts with TAX1BP1 to disrupt the Itch, RNF11, NRP and A20 complex to potentiate and sustain NF-κB activation. Cell adhesion molecule 1 (CADM1) interaction with Tax also facilitates Ubc13-mediated K63-linked polyubiquitination of Tax and NF-κB activation. Tax interacts with HSP90 for protection against proteasomal degradation mediated by PDLIM2-triggered K48-linked polyubiquitination in the nuclear matrix. Tax is also monoubiquitinated upon genotoxic stress to trigger its nuclear export in a CRM-1-dependent manner. SUMOylation of Tax is mediated by Ubc9 and SUMOylated Tax is found in nuclear bodies. Acetylated Tax also interacts with p300 in the nucleus. Tax interacts with TRAF6 to stabilize MCL-1 through K63-linked polyubiquitination in mitochondria, and its interaction with USP10 leads to increased reactive oxygen species (ROS) production to inhibit apoptosis. Tax also interacts with CREB-activating transcription factor family protein (CREB/ATF) and recruits CBP/300 to the long terminal repeat (LTR) for trans-activation of the viral promoter. The NF-κB canonical pathway is indicated by solid black lines with arrows. The noncanonical NF-κB pathway is indicated by solid red lines with arrows.