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Publication : Parkin negatively regulates the antiviral signaling pathway by targeting TRAF3 for degradation.

First Author  Xin D Year  2018
Journal  J Biol Chem Volume  293
Issue  31 Pages  11996-12010
PubMed ID  29903906 Mgi Jnum  J:267103
Mgi Id  MGI:6197364 Doi  10.1074/jbc.RA117.001201
Citation  Xin D, et al. (2018) Parkin negatively regulates the antiviral signaling pathway by targeting TRAF3 for degradation. J Biol Chem 293(31):11996-12010
abstractText  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 Lys(48)-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.
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