1. Academic Validation
  2. BICP0 Negatively Regulates TRAF6-Mediated NF-κB and Interferon Activation by Promoting K48-Linked Polyubiquitination of TRAF6

BICP0 Negatively Regulates TRAF6-Mediated NF-κB and Interferon Activation by Promoting K48-Linked Polyubiquitination of TRAF6

  • Front Microbiol. 2020 Jan 8;10:3040. doi: 10.3389/fmicb.2019.03040.
Chong Cao 1 Ran An 1 YueYang Yu 1 HaiYue Dai 1 ZheHui Qu 1 MingChun Gao 1 JunWei Wang 1
Affiliations

Affiliation

  • 1 Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
Abstract

The infected cell protein 0 (BICP0) is an immediate early protein encoded by BHV-1, and its RING finger domain, which endows BICP0 with intrinsic E3 ubiquitin Ligase activity, is common in all ICP0 proteins. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is one of the TRAF family members and is ubiquitously expressed in mammalian tissues. TRAF6 forms the MyD88-TRAF6-IRF7 complex and activates interferon induction in the TLR (Toll-like receptors) and the RLR (RIG-I-like Receptor) pathway. Previous studies showed that BICP0 reduced IFN-β promoter activity by interacting with IRF7. In this study, we found that BICP0 promoted the K48-ubiquitination and degradation of TRAF6 through the ubiquitin Proteasome system. The interaction between BICP0 and TRAF6 is a prerequisite for ubiquitination modification, and the 346-PAERQY-351 of BICP0 is indispensable. The motif mutation experiments showed that the tyrosine 351 of BICP0 is the key amino acid involved. Further studies demonstrated that BICP0 suppressed the NF-κB pathway via the interference of TRAF6. Moreover, degradation of TRAF6 protein influenced the K63-linked ubiquitination of IRF7 and activation of interferon promoter. Collectively, these findings indicate that the BICP0 protein suppresses the inflammation signaling and IFN production by K48-linked polyubiquitination of TRAF6 and may further clarify the immune evasion function of BICP0.

Keywords

BICP0; NF-κB; TRAF6; interferon; motif; ubiquitin.

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