Back

Novel functions of Kaposi's sarcoma herpesvirus viral FLICE inhibitory protein

Herold, K.; Ruffin, A.; Moorad, R.; Constantine, M.; Causey, A.; Mitchell, A. E.; Chmura, J. C.; Ehrlich, E. S.

2022-05-31 microbiology
10.1101/629113 bioRxiv
Show abstract

KSHV viral FLICE inhibitory protein (vFLIP) is a potent activator of NF-{kappa}B signaling and an inhibitor of apoptosis and autophagy. Inhibition of vFLIP function and NF-{kappa}B signaling promotes lytic reactivation. Here we provide evidence for a novel function of vFLIP in promoting NF{kappa}B signaling through inhibition of the DUB activity of the negative regulator, A20. We demonstrate interaction of vFLIP with the Itch/A20 ubiquitin editing complex. We have identified a SUMO interaction motif in vFLIP that is required for NF-{kappa}B activation. Mutation of the SIM in BAC16 resulted in increased spontaneous RTA expression and loss of spindle cell morphology. Our results suggest a role for SUMO in mediating vFLIP function and provide evidence for vFLIP modulation of the negative regulation of NF-{kappa}B signaling by A20. Our results provide further insight into the function of vFLIP and SUMO in the regulation of NF-{kappa}B signaling and the latent lytic transition.

Matching journals

The top 2 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.