Dynamic RBM47 ISGylation confers broad immunoprotection against lung injury and tumorigenesis via TSC22D3 downregulation.

ABSTRACT: ISGylation is a well-established antiviral mechanism, but its specific function in immune and tissue homeostasis regulation remains elusive. Here, we reveal that the RNA-binding protein RBM47 undergoes phosphorylation-dependent ISGylation at lysine 329 to regulate immune activation and maintain lung homeostasis. K329R knockin (KI) mice with defective RBM47-ISGylation display heightened susceptibility to LPS-induced acute lung injury and lung tumorigenesis, accompanied with multifaceted immunosuppression characterized by elevated pro-inflammatory factors, reduced IFNs/related chemokines, increased myeloid-derived suppressor cells, and impaired tertiary lymphoid structures. Mechanistically, RBM47-ISGylation regulation of the expression of TSC22D3 mRNA, a glucocorticoid-inducible transcriptio

SUBMITTER: Ding S 

PROVIDER: S-EPMC10689852 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature