Site-specific ubiquitination of the E3 ligase HOIP regulates apoptosis and immune signaling.

ABSTRACT: HOIP, the catalytic component of the linear ubiquitin chain assembly complex (LUBAC), is a critical regulator of inflammation. However, how HOIP itself is regulated to control inflammatory responses is unclear. Here, we discover that site-specific ubiquitination of K784 within human HOIP promotes tumor necrosis factor (TNF)-induced inflammatory signaling. A HOIP K784R mutant is catalytically active but shows reduced induction of an NF-κB reporter relative to wild-type HOIP. HOIP K784 is evolutionarily conserved, equivalent to HOIP K778 in mice. We generated Hoip^K778R/K778R knock-in mice, which show no overt developmental phenotypes; however, in response to TNF, Hoip^K778R/K778R mouse embryonic fibroblasts display mildly suppressed NF-κB activation and increased apoptot

SUBMITTER: Fennell LM 

PROVIDER: S-EPMC7737615 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature