Postranslation protein modification via addition of the high

Postranslation protein modification via addition of the highly conserved ubiquitin to substrate proteins by E1, E2 and E3 enzymes occurs frequently in eukaryotic Conessine (Popovic et al., 2014, van Wijk and Timmers, 2010). Poly-ubiquitination usually targets the substrate proteins for destruction by the 26S proteasome. Alternatively, ubiquitination, especially mono- and multi-ubiquitination alters the biochemical properties and subcellular localization of substrate proteins (Popovic et al., 2014, van Wijk and Timmers, 2010). Ubiqutination also greatly affects the functions of many viral proteins and viruses actively manipulate the ubiquitin network to suppress innate immunity (Alcaide-Loridan and Jupin, 2012, Lindner, 2007, Okumura et al., 2006, Shackelford and Pagano, 2004, Shackelford and Pagano, 2005, Taylor and Barry, 2006). The yeast Rad6p (radiation sensitive 6, also called Ubc2) E2 ubiquitin-conjugating enzyme is a member of the highly conserved UBC proteins in eukaryotes (Xu et al., 2009). Rad6p is involved in several cellular processes, including DNA repair, transcriptional activation and silencing, histone ubiquitination, ubiquitin-mediated N-end rule protein degradation and endoplasmic reticulum-associated protein degradation (ERAD) (Popovic et al., 2014, van Wijk and Timmers, 2010). Mutations in RAD6 homologs are involved in many diseases (Popovic et al., 2014). In Arabidopsis, 37 proteins with a UBC domain and active-site cysteine have been predicted. Among these Arabidopsis UBC proteins, the best-characterized RAD6 homolog is AtUBC2 (Xu et al., 2009). AtUBC2 can partially rescue the UV-sensitivity and slow growth of rad6Δ yeast (Zwirn et al., 1997). AtUbc2p has E2 activity in vitro and has been shown to mono-ubiquitinate substrates in the absence of E3 ubiquitin ligases (Strzalka et al., 2013). UBC2 is proposed to affect DNA repair, histone ubiquitination, flowering time, and enhance salt and drought-tolerance and modulate abiotic stress-induced gene expression in plants (Cao et al., 2008, Qin, 2013, Xu et al., 2009). TBSV is a small (+)RNA virus that has been intensively used to study virus replication, recombination, and virus – host interactions based on yeast (Saccharomyces cerevisiae) model host (Nagy and Pogany, 2006, Nagy and Pogany, 2012, Nagy et al., 2014, Panavas and Nagy, 2003, Panaviene et al., 2004, White and Nagy, 2004). The auxiliary p33 replication protein, which is an RNA chaperone, recruits the TBSV (+)RNA to the cytosolic surface of peroxisomal membranes for replication (Jonczyk et al., 2007, McCartney et al., 2005, Nagy et al., 2012, Panavas et al., 2005a, Pogany et al., 2005, Stork et al., 2011). The interaction between the viral p33 and p92pol RdRp protein is required for assembling the functional VRC (Panavas et al., 2005a, Panaviene et al., 2004, Panaviene et al., 2005, Pogany and Nagy, 2008, Pogany and Nagy, 2012). The assembly and functions of VRCs are also affected by host components, such as the host heat shock protein 70 (Hsp70), the eukaryotic elongation factor 1A (eEF1A), ESCRT (endosomal sorting complexes required for transport) proteins and sterols and phospholipids (Li et al., 2008, Li and Nagy, 2011, Li et al., 2009, Li et al., 2010, Pogany and Nagy, 2012, Pogany and Nagy, 2015, Pogany et al., 2008, Serva and Nagy, 2006, Sharma et al., 2010, Sharma et al., 2011, Wang et al., 2009a, Wang et al., 2009b, Xu and Nagy, 2015).