Novel functions of Kaposi’s sarcoma herpesvirus viral FLICE inhibitory protein
| Autor: | Kevin Herold, Ayana Ruffin, Mathew Constantine, Amerria Causey, Ashley E. Mitchell, Jennifer C. Chmura, Razia Moorad, Elana S. Ehrlich |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
biology Activator (genetics) Chemistry Autophagy SUMO protein Inhibitor of apoptosis Small molecule Virus 3. Good health Cell biology 03 medical and health sciences 0302 clinical medicine Ubiquitin Lytic cycle 030220 oncology & carcinogenesis biology.protein 030304 developmental biology |
| DOI: | 10.1101/629113 |
| Popis: | KSHV 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 viral 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. We observed a decrease in vFLIP induced NF{kappa}B when the SIM in vFLIP was mutated. Small molecule inhibition of SUMOylation resulted in a dose dependent increase lytic reactivation and virus production. 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. |
| Databáze: | OpenAIRE |
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