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The multifaceted role of the E3 ubiquitin ligase HOIL ‐1: beyond linear ubiquitination
Author(s) -
Elton Lynn,
Carpentier Isabelle,
Verhelst Kelly,
Staal Jens,
Beyaert Rudi
Publication year - 2015
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12307
Subject(s) - ubiquitin ligase , ubiquitin , biology , inflammation , signal transduction , microbiology and biotechnology , immunology , cancer research , genetics , gene
Summary Ubiquitination controls and fine‐tunes many signaling processes driving immunity, inflammation, and cancer. The E3 ubiquitin ligase HOIL ‐1 (heme‐oxidized IRP 2 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.