Leveraging SUMOylation To Regulate Immune Response

Introduction

The small ubiquitin-like modifier 1 (SUMO1) was first identified in 1997¹ and since then, several isoforms (SUMO2, SUMO3, SUMO4, SUMO5), the SUMO enzymatic machinery (E1, E2, E3), and de-SUMOylases (SENPs) have been identified and characterized^{(reviewed in 2)} (see Figure 1).  Furthermore, it has been shown that this critical post-translational modification can selectively modify thousands of target proteins in a regulated fashion to control the protein’s localization, stability, and function; thereby, modulating critically important cellular processes like DNA repair, stress response, cellular trafficking, and many others^{(reviewed in 2)}. Thus, it is not surprising that dysregulation of SUMOylation has been linked to many diseases including cancer. There are many examples where dysregulation of SUMOylation acts on the cancer cell directly to augment its proliferation, migration, and metastasis ^{(reviewed in 3)} . Of equal importance, there is compelling evidence that SUMOylation facilitates cancer progression by modifying the tumor microenvironment and disrupting normal immune surveillance. In this newsletter, the effects of SUMOylation on the immune cells in both cancer and host immune responses are discussed.