Kaposi’s sarcoma herpesvirus viral FLICE inhibitory protein modulates A20 deubiquitinase activity

Abstract

KSHV viral FLICE inhibitory protein (vFLIP) is a potent activator of NF-κB signaling and an inhibitor of apoptosis and autophagy. Inhibition of vFLIP function and NF-κB signaling promotes lytic reactivation. Here we provide evidence for a novel function of vFLIP through inhibition of the deubiquitinating (DUB) activity of the negative regulator, A20. We demonstrate direct interaction of vFLIP with the Itch/A20 ubiquitin editing complex and provide evidence for subsequent loss of A20 DUB activity. Our results provide further insight into the function of vFLIP in the regulation of NF-κB signaling.