The SUMO conjugation system regulates key cellular processes including cell growth, division, mitochondrial dynamics, and the maintenance of genome stability in eukaryotic cells. The ubiquitin conjugation system regulates the stability of a myriad of vital cellular proteins in a signal-dependent manner by targeting them for destruction via the proteasome-mediated degradation pathway. Recent research efforts have unveiled an evolutionarily conserved and fundamental molecular interface between the SUMO and ubiquitin systems. A coordinated and integrated interaction between these two pathways plays a key role in adapting the SUMO-related stress response to alterations in sub-cellular protein localization, specific protein recruitment strategies, and the regulation of stress-inducible protein stability. This chapter will describe the interconnected and interdependent role of the SUMO and ubiquitin systems in mediating DNA damage repair and the genesis and the resolution of inflammatory-related diseases such as cancer. New insights regarding the interdependence of these two important post-translational modifications with nuclear receptor superfamily members will also be highlighted.
Keywords: DNA damage repair; Inflammatory-related disease; RNF4; STUbls.