Ubiquitin acetylation inhibits polyubiquitin chain elongation |
| |
| Authors: | Fumiaki Ohtake Yasushi Saeki Kensaku Sakamoto Kazumasa Ohtake Hiroyuki Nishikawa Hikaru Tsuchiya Tomohiko Ohta Keiji Tanaka Jun Kanno |
| |
| Affiliation: | 1. Division of Cellular and Molecular Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Setagaya‐ku, Tokyo, Japan;2. Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Sciences, Setagaya‐ku, Tokyo, Japan;3. Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, Tsurumi, Yokohama, Japan;4. Institute of Advanced Medical Science, St. Marianna University Graduate School of Medicine, Kawasaki, Japan;5. Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, Japan |
| |
| 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. |
| |
| Keywords: | acetylation mechanism post-translational modification ubiquitin |
|
|
