KAPOSI’S SARCOMA-ASSOCIATED HERPESVIRUS PROTEIN, KAPOSIN B INDUCES THE SELECTIVE CATABOLISM OF PROCESSING BODIES
Singh, Gillian Kristina
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Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of the inflammatory endothelial cell (EC) cancer, Kaposi’s Sarcoma (KS). Many inflammatory mRNAs (ARE-mRNAs) are subject to constitutive decay in cytoplasmic ribonucleoprotein granules called processing bodies (PB). The viral protein KapB contributes to this inflammatory phenotype by inducing PB disassembly and a correlative increase in ARE-mRNA stabilization. However, the precise molecular mechanism governing KapB-mediated PB disassembly is unclear. My research uncovered a novel link between selective autophagy (SA) and PB disassembly. During SA, molecular-adapter proteins, such as NDP52, selectively bind and target cargo for degradation. I found that KapB-mediated PB disassembly and stabilization of a reporter ARE-mRNA requires NDP52. Moreover, overexpression of authentic NDP52, but not mutated NDP52, rescued KapB-mediated PB disassembly in the context of NDP52 knockdown. Collectively, these data suggest KapB hijacks SA machinery to disassemble PBs, thus contributing to the proinflammatory environment beneficial for tumourigenesis.