title: Research progress in linear ubiquitin modification.
abstract: Protein ubiquitination plays vital roles in regulating various cytobiological processes such as cell cycle progression, DNA damage repair, signal transduction and membrane localization of various proteins. Moreover, proteins can be modified by single ubiquitin molecules (monoubiquitination) or ubiquitin chains (polyubiquitination). Polyubiquitination regulates protein function by linking different types of polyubiquitin chains to substrates. All the 7 known linkage types of polyubiquitination are inter-ubiquitin linkages formed through lysine residues. In recent years, the eighth ubiquitin linkage type, linear ubiquitination in which the linkages are formed between the amino group of methionine residues of ubiquitin and the carboxy group of glycine residues of another, has been identified. Studies have shown that linear ubiquitination plays very important roles in various processes including innate immunity and inflammatory reactions. The ubiquitin ligase E3 that recruits linear ubiquitin chains is called linear ubiquitin chain assembly complex (LUBAC), however, little is known about its constitutive substrates, activity regulation and functions. Here we reviewed the mechanism of activity regulation of ubiquitin ligases, deubiquitinating enzymes and substrates as well as their roles in multiple areas including innate immunity, and also analyzed future directions to provide references for relevant studies.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Shan
authors.initials: S
authors.lastname: He
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Ling-qiang
authors.initials: LQ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D010450:Endopeptidases / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D016328:NF-kappa B / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology; D054875:Ubiquitination
chemical_list: D016328:NF-kappa B; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D010450:Endopeptidases; C582107:OTULIN protein, human