Reference - Detail
| RRC ID | 89563 |
|---|---|
| Author | Okuda C, Tokumori S, Vu NT, Muroi M, Sanada E, Suzuki T, Dohmae N, Osada H, Shiono Y, Kimura KI, Kumada Y, Shiba T, Komada M, Fukushima T, Kataoka T. |
| Title | Allantopyrone A promotes cross-linking of ubiquitin-specific protease 5 (USP5) and inhibits its deubiquitinase activity by targeting distinct domains. |
| Journal | J Antibiot (Tokyo) |
| Abstract |
Allantopyrone A is an α-pyrone metabolite produced by the plant endophytic fungus Allantophomopsis lycopodina KS-97. We previously demonstrated that allantopyrone A decreased the abundance of many components of 26S proteasome fractions while inducing the appearance of an additional protein with a higher apparent molecular mass than known proteasome components. In the present study, we identified this protein as ubiquitin-specific protease 5 (USP5) using mass spectrometry. In cell-based assays, allantopyrone A promoted the cross-linked form of USP5, which was shown by immunoprecipitation to represent a USP5 dimer. The cross-linked form of USP5 was markedly reduced when the C-terminal zinc finger ubiquitin-binding domain (cUBP; residues 175-283) was deleted or when Cys195 was substituted with alanine. Allantopyrone A was also found to reduce the activity of multiple deubiquitinases. USP5 labeling by ubiquitin-vinyl methyl ester was markedly reduced by allantopyrone A or by a Cys335 substitution. Consistent with these biological effects of allantopyrone A on USP5, in silico docking studies suggested that allantopyrone A interacts with Cys195 on the surface of the cUBP domain and is positioned near Cys335 within the catalytic center of the USP domain. These results demonstrate that allantopyrone A promotes USP5 cross-linking and inhibits its deubiquitinase activity through interactions with distinct domains. |
| Published | 2026-7-14 |
| DOI | 10.1038/s41429-026-00948-6 |
| PII | 10.1038/s41429-026-00948-6 |
| PMID | 42449145 |
| Resource | |
| Human and Animal Cells | 293T(RCB2202) |