Sensing and responding to cytosolic viruses invasions: An orchestra of kaleidoscopic ubiquitinations

Ubiquitin is a versatile molecular signature that modulates diverse cellular processes via proteasome-dependent and proteasome-independent mechanisms. The covalent and/or non-covalent binding of mono-ubiquitin and/or poly-ubiquitin chains to a target protein broadens the dynamic and functional spectra for signal integration. Different linkages of poly-ubiquitin chains determine specific physiological or pathological functions of target proteins. Accumulating evidences has revealed the essential roles of ubiquitination in orchestrating the host defenses against cytosolic RNA or DNA from viral infections. In this review, we summarize the current progress regarding the understanding of ubiquitin-mediated regulation of the RIG-I and STING antiviral signaling pathways and discuss certain critical issues that remain to be resolved in future studies.