MDA5 ISGylation is crucial for immune signaling to control viral replication and pathogenesis.

ABSTRACT: The posttranslational modification (PTM) of innate immune sensor proteins by ubiquitin or ubiquitin-like proteins is crucial for regulating antiviral host responses. The cytoplasmic dsRNA receptor melanoma differentiation-associated protein 5 (MDA5) undergoes several PTMs including ISGylation within its first caspase activation and recruitment domain (CARD), which promotes MDA5 signaling. However, the relevance of MDA5 ISGylation for antiviral immunity in an infected organism has been elusive. Here, we generated knock-in mice (MDA5 ^K23R/K43R ) in which the two major ISGylation sites, K23 and K43, in MDA5 were mutated. Primary cells derived from MDA5 ^K23R/K43R mice exhibited abrogated endogenous MDA5 ISGylation and an impaired ability of MDA

SUBMITTER: Sarkar L 

PROVIDER: S-EPMC11463472 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature