The Role of SUMOylation in the KSHV Kaposin B-MK2 Signaling Axis

Abstract

Kaposi’s sarcoma (KS) is characterized by infection with Kaposi’s sarcoma associated herpesvirus (KSHV), aberrant inflammation and cell spindling. These phenotypes are recapitulated by expression of the viral gene product Kaposin B (KapB). KapB binds and activates the kinase MK2, which is required for both effects; how KapB activates MK2 is not known. MK2 is modified by SUMOylation and preventing SUMOylation enhanced MK2 activity. Therefore, I hypothesized that KapB disrupts MK2 SUMOylation. I confirmed MK2 SUMOylation and discovered that constitutively active MK2 is hyper-SUMOylated compared to wild type, suggesting that SUMOylation may be phosphorylation directed. However, the co-expression KapB did not alter the MK2 SUMOylation profile in this assay. I observed that overexpressed MK2 constructs stabilized ARE-mRNAs and disassembled PBs. My work uncovered a regulatory interplay between phosphorylation and SUMOylation which may provide insight into the regulation of inflammatory responses by MK2 during cellular stress, such as latent KSHV infection and tumourigenesis.