PT  - JOURNAL ARTICLE
AU  - Ayesha M. Patel
AU  - E. Neil G. Marsh
TI  - The Antiviral Enzyme, Viperin, Activates Protein Ubiquitination by the E3 Ubiquitin Ligase, TRAF6
AID  - 10.1101/2021.02.21.432004
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.21.432004
4099  - http://biorxiv.org/content/early/2021/02/22/2021.02.21.432004.short
4100  - http://biorxiv.org/content/early/2021/02/22/2021.02.21.432004.full
AB  - Viperin is a broadly conserved radical SAM enzyme that synthesizes the antiviral nucleotide ddhCTP. In higher animals viperin expression also accelerates the degradation of various cellular and viral proteins necessary for viral replication; however, the details of this process remain largely unknown. Here we show that viperin activates a component of the protein ubiquitination machinery, which plays an important role in both protein degradation and immune signaling pathways. We demonstrate that viperin binds the E3 ubiquitin ligase, TRAF6, which catalyzes K63-linked ubiquitination associated with immune signaling pathways. Viperin activates ubiquitin transfer by TRAF6 ~2.5-fold and causes a significant increase in polyubiquitinated forms of TRAF6 that are important for mediating signal transduction. Our observations both imply a role for viperin as an agonist of immune signaling and suggest that viperin may activate other K48-linked E3-ligases involved in targeting proteins for proteasomal degradation.Competing Interest StatementThe authors have declared no competing interest.