title: A ubiquitin ligase complex assembles linear polyubiquitin chains.
abstract: The ubiquitin system plays important roles in the regulation of numerous cellular processes by conjugating ubiquitin to target proteins. In most cases, conjugation of polyubiquitin to target proteins regulates their function. In the polyubiquitin chains reported to date, ubiquitin monomers are linked via isopeptide bonds between an internal Lys and a C-terminal Gly. Here, we report that a protein complex consisting of two RING finger proteins, HOIL-1L and HOIP, exhibits ubiquitin polymerization activity by recognizing ubiquitin moieties of proteins. The polyubiquitin chain generated by the complex is not formed by Lys linkages, but by linkages between the C- and N-termini of ubiquitin, indicating that the ligase complex possesses a unique feature to assemble a novel head-to-tail linear polyubiquitin chain. Moreover, the complex regulates the stability of Ub-GFP (a GFP fusion protein with an N-terminal ubiquitin). The linear polyubiquitin chain generated post-translationally may function as a new modulator of proteins.
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Kirisako
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kamei
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murata
authors.forename: Michiko
authors.initials: M
authors.lastname: Kato
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fukumoto
authors.forename: Masato
authors.initials: M
authors.lastname: Kanie
authors.forename: Soichi
authors.initials: S
authors.lastname: Sano
authors.forename: Fuminori
authors.initials: F
authors.lastname: Tokunaga
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iwai
mesh_terms: D006367:HeLa Cells; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D014157:Transcription Factors; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D014157:Transcription Factors; D025801:Ubiquitin; C504507:RBCK1 protein, human; D044767:Ubiquitin-Protein Ligases