AI Article Synopsis
- HACE1 is identified as a key negative regulator in the signaling pathway triggered by virus infections, which controls the production of proinflammatory cytokines.
- Overexpressing HACE1 reduces type I interferon (IFN) signaling and enhances virus replication, while knocking down HACE1 has the opposite effect.
- HACE1 functions downstream of MAVS and upstream of TBK1, inhibiting virus-induced signaling by disrupting the MAVS-TRAF3 complex, highlighting its new role in regulating innate immunity.
Article Abstract
During virus infection, the cascade signaling pathway that leads to the production of proinflammatory cytokines is controlled at multiple levels to avoid detrimental overreaction. HACE1 has been characterized as an important tumor suppressor. Here, we identified HACE1 as an important negative regulator of virus-triggered type I IFN signaling. Overexpression of HACE1 inhibited Sendai virus- or poly (I:C)-induced signaling and resulted in reduced IFNB1 production and enhanced virus replication. Knockdown of HACE1 expression exhibited the opposite effects. Ubiquitin E3 ligase activity of the dead mutant HACE1/C876A had a comparable inhibitory function as WT HACE1, suggesting that the suppressive function of HACE1 on virus-induced signaling is independent of its E3 ligase activity. Further study indicated that HACE1 acted downstream of MAVS and upstream of TBK1. Mechanistic studies showed that HACE1 exerts its inhibitory role on virus-induced signaling by disrupting the MAVS-TRAF3 complex. Therefore, we uncovered a novel function of HACE1 in innate immunity regulation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885101 | PMC |
| http://dx.doi.org/10.3390/v8050146 | DOI Listing |
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