The ubiquitin ligase HOIL-1L regulates immune responses by interacting with linear ubiquitin chains.

ABSTRACT: The Linear Ubiquitin Chain Assembly Complex (LUBAC), composed of HOIP, HOIL-1L, and SHARPIN, promotes tumor necrosis factor (TNF)-dependent NF-κB signaling in diverse cell types. HOIL-1L contains an Npl4 Zinc Finger (NZF) domain that specifically recognizes linear ubiquitin chains, but its physiological role in vivo has remained unclear. Here, we demonstrate that the HOIL-1L NZF domain has important regulatory functions in inflammation and immune responses in mice. We generated knockin mice (Hoil-1l ^{T201A;R208A/T201A;R208A} ) expressing a HOIL-1L NZF mutant and observed attenuated responses to TNF- and LPS-induced shock, including prolonged survival, stabilized body temperature, reduced cytokine production, and liver damage markers. Cells derived from Hoil

SUBMITTER: Gomez-Diaz C 

PROVIDER: S-EPMC8561004 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature