Sec10 suppresses antiviral innate immune response by facilitating STUB1-mediated STAT1 degradation.

ABSTRACT: The exocyst complex is a heterooctameric protein complex, the individual components of the complex are thought to act on specific biological processes. However, the role of Sec10, the central subunit of the complex, in host defense and viral replication remains unclear. Here, we reported that Sec10 significantly impairs the activation of JAK-STAT signal pathway of type I IFN (IFN-I) response against both DNA- and RNA-viruses, and promotes viral replication, respectively. Mechanistically, Sec10 interacts with E3 ligase STUB1, promotes the interaction of STUB1 and STAT1, and consequently accelerate STUB1-mediated proteasomal degradation of STAT1 via K6-linked polyubiquitination at Lys240 and Lys652, thus weakens STAT1 triggered antiviral immune responses. More importantly, myeloid-specific d

SUBMITTER: Sun F 

PROVIDER: S-EPMC12425391 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature