Abstract
Chronic neuroinflammation is a characteristic of Parkinson's disease (PD). Previous investigations have shown that Parkin gene mutations are related to the early-onset recessive form of PD and isolated juvenile-onset PD. Further, Parkin plays important roles in mitochondrial quality control and cytokine-induced cell death. However, whether Parkin regulates other cellular events is still largely unknown. In this study, we performed overexpression and knockout experiments and found that Parkin negatively regulates antiviral immune responses against RNA and DNA viruses. Mechanistically, we show that Parkin interacts with tumor necrosis factor receptor-associated factor 3 (TRAF3) to regulate stability of TRAF3 protein by promoting Lys48-linked ubiquitination. Our findings suggest that Parkin plays a novel role in innate immune signaling by targeting TRAF3 for degradation and maintaining the balance of innate antiviral immunity.
Highlights
Chronic neuroinflammation is a characteristic of Parkinson’s disease (PD)
Previous investigations have shown that Parkin gene mutations are related to the early-onset recessive form of PD and isolated juvenile-onset PD
Whether Parkin is involved in other cellular events is still largely unknown
Summary
Chronic neuroinflammation is a characteristic of Parkinson’s disease (PD). Previous investigations have shown that Parkin gene mutations are related to the early-onset recessive form of PD and isolated juvenile-onset PD. In agreement with a negative role of Parkin in antiviral signaling, we found that Parkin overexpression significantly decreased levels of IRF3 phosphorylation and dimerization induced by SeV infection (Fig. 1E). QRT–PCR assays showed that after SeV infection, Parkin knockout significantly increased transcript levels of Ifnb1 and IFN-stimulated cytokine genes, such as interferon-induced protein with tetratricopeptide repeats 1 (Ifit1), compared with WT controls (Fig. 2, A and B).
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