UNC13D inhibits STING signaling by attenuating its oligomerization on the endoplasmic reticulum.

ABSTRACT: Stimulator of interferon genes (STING) is an essential signaling protein that is located on the endoplasmic reticulum (ER) and triggers the production of type I interferons (IFN) and proinflammatory cytokines in response to pathogenic DNA. Aberrant activation of STING is linked to autoimmune diseases. The mechanisms underlying homeostatic regulation of STING are unclear. Here, we report that UNC13D, which is associated with familial hemophagocytic lymphohistiocytosis (FHL3), is a negative regulator of the STING-mediated innate immune response. UNC13D colocalizes with STING on the ER and inhibits STING oligomerization. Cellular knockdown and knockout of UNC13D promote the production of interferon-β (IFN-β) induced by DNA viruses, but not RNA viruses. Moreover, UNC13D deficiency also increas

SUBMITTER: Song P 

PROVIDER: S-EPMC9638857 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature