title: The multifaceted role of the E3 ubiquitin ligase HOIL-1: beyond linear ubiquitination.
abstract: Ubiquitination controls and fine-tunes many signaling processes driving immunity, inflammation, and cancer. The E3 ubiquitin ligase HOIL-1 (heme-oxidized IRP2 ubiquitin ligase-1) is increasingly implicated in different signaling pathways and plays a vital role in immune regulation. HOIL-1 co operates with the E3 ubiquitin ligase HOIP (HOIL-1 interacting protein) to modify specific nuclear factor-κB (NF-κB) signaling proteins with linear M1-linked polyubiquitin chains. In addition, through its ability to also add K48-linked polyubiquitin chains to specific substrates, HOIL-1 has been linked with antiviral signaling, iron and xenobiotic metabolism, cell death, and cancer. HOIL-1 deficiency in humans leads to myopathy, amylopectinosis, auto-inflammation, and immunodeficiency associated with an increased frequency of bacterial infections. HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium, pathogen-specific immunodeficiency, but minimal signs of hyper-inflammation. This review summarizes current knowledge on the mechanism of action of HOIL-1 and highlights recent advances regarding its role in health and disease.
authors.affiliation: Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Lynn
authors.initials: L
authors.lastname: Elton
authors.affiliation: Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Carpentier
authors.affiliation: Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Kelly
authors.initials: K
authors.lastname: Verhelst
authors.affiliation: Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Jens
authors.initials: J
authors.lastname: Staal
authors.affiliation: Inflammation Research Center, Unit of Molecular Signal Transduction in Inflammation, VIB, Ghent, Belgium.|Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Rudi
authors.initials: R
authors.lastname: Beyaert
mesh_terms: D000818:Animals; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B; D015398:Signal Transduction; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D016328:NF-kappa B; D014157:Transcription Factors; C504507:RBCK1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: HOIL-1; RBCK1; cancer; immunity; metabolism; ubiquitination