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

TL;DR

This study reveals a new role of a virus protein in blocking a key enzyme that controls cell signaling and survival.

Contribution

The paper identifies a novel mechanism by which vFLIP inhibits A20's deubiquitinase activity, affecting NF-κB signaling.

Findings

vFLIP directly interacts with Itch and A20, inhibiting A20's deubiquitinase activity.

Inhibition of vFLIP function promotes lytic reactivation of KSHV.

The findings enhance understanding of vFLIP's role in regulating NF-κB signaling.

Abstract

KSHV viral FLICE inhibitory protein (vFLIP) is a potent activator of NF-κB signalling and an inhibitor of apoptosis and autophagy. Inhibition of vFLIP function and NF-κB signalling 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 Itch and A20 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 signalling.

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