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Ubiquitin acetylation inhibits polyubiquitin chain elongation
Author(s) -
Ohtake Fumiaki,
Saeki Yasushi,
Sakamoto Kensaku,
Ohtake Kazumasa,
Nishikawa Hiroyuki,
Tsuchiya Hikaru,
Ohta Tomohiko,
Tanaka Keiji,
Kanno Jun
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201439152
Subject(s) - ubiquitin , acetylation , ubiquitin conjugating enzyme , microbiology and biotechnology , lysine , deubiquitinating enzyme , biology , histone , biochemistry , histone h2b , ubiquitin ligase , ubiquitin protein ligases , chemistry , dna , amino acid , gene
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 K 48. Acetylated ubiquitin does not affect substrate monoubiquitylation, but inhibits K 11‐, K 48‐, and K 63‐linked polyubiquitin chain elongation by several E 2 enzymes in vitro . In cells, A cK6‐mimetic ubiquitin stabilizes the monoubiquitylation of histone H 2 B —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.