title: Ubiquitin acetylation inhibits polyubiquitin chain elongation.
abstract: Ubiquitylation is a versatile post-translational modification (PTM). The diversity of ubiquitylation topologies, which encompasses different chain lengths and linkages, underlies its widespread cellular roles. Here, we show that endogenous ubiquitin is acetylated at lysine (K)-6 (AcK6) or K48. Acetylated ubiquitin does not affect substrate monoubiquitylation, but inhibits K11-, K48-, and K63-linked polyubiquitin chain elongation by several E2 enzymes in vitro. In cells, AcK6-mimetic ubiquitin stabilizes the monoubiquitylation of histone H2B-which we identify as an endogenous substrate of acetylated ubiquitin-and of artificial ubiquitin fusion degradation substrates. These results characterize a mechanism whereby ubiquitin, itself a PTM, is subject to another PTM to modulate mono- and polyubiquitylation, thus adding a new regulatory layer to ubiquitin biology.
authors.affiliation: Division of Cellular and Molecular Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Setagaya-ku Tokyo, Japan ohtake@nihs.go.jp.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Ohtake
authors.affiliation: Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Sciences, Setagaya-ku Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saeki
authors.affiliation: Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, Tsurumi Yokohama, Japan.
authors.forename: Kensaku
authors.initials: K
authors.lastname: Sakamoto
authors.affiliation: Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, Tsurumi Yokohama, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Ohtake
authors.affiliation: Institute of Advanced Medical Science, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishikawa
authors.affiliation: Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Sciences, Setagaya-ku Tokyo, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Tsuchiya
authors.affiliation: Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ohta
authors.affiliation: Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Sciences, Setagaya-ku Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Division of Cellular and Molecular Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Setagaya-ku Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
mesh_terms: D000107:Acetylation; D006801:Humans; D025821:Polyubiquitin / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D025801:Ubiquitin; D025821:Polyubiquitin
keywords: acetylation; mechanism; post‐translational modification; ubiquitin