Allantopyrone A promotes cross-linking of ubiquitin-specific protease 5 (USP5) and inhibits its deubiquitinase activity by targeting distinct domains.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	Allantopyrone A promotes cross-linking of ubiquitin-specific protease 5 (USP5) and inhibits its deubiquitinase activity by targeting distinct domains.
Συγγραφείς:	Okuda C; Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan., Tokumori S; Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan., Vu NT; Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan., Muroi M; Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science, Saitama, Japan.; Chemical Resource Development Research Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science, Saitama, Japan., Sanada E; Chemical Resource Development Research Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science, Saitama, Japan., Suzuki T; Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science, Saitama, Japan., Dohmae N; Biomolecular Characterization Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science, Saitama, Japan., Osada H; Chemical Resource Development Research Unit, Technology Platform Division, RIKEN Center for Sustainable Resource Science, Saitama, Japan.; Institute of Microbial Chemistry (BIKAKEN), Shinagawa, Japan., Shiono Y; Department of Food, Life, and Environmental Science, Faculty of Agriculture, Yamagata University, Yamagata, Japan., Kimura KI; The United Graduate School of Agricultural Sciences, Iwate University, Iwate, Japan., Kumada Y; Department of Functional Chemistry and Engineering, Kyoto Institute of Technology, Kyoto, Japan., Shiba T; Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan., Komada M; Cell Biology Center, Institute of Integrated Research, Institute of Science Tokyo, Yokohama, Japan., Fukushima T; Cell Biology Center, Institute of Integrated Research, Institute of Science Tokyo, Yokohama, Japan., Kataoka T; Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan. takao.kataoka@kit.ac.jp.; Center for Social and Biomedical Engineering, Kyoto Institute of Technology, Kyoto, Japan. takao.kataoka@kit.ac.jp.
Πηγή:	The Journal of antibiotics [J Antibiot (Tokyo)] 2026 Oct; Vol. 79 (10), pp. 673-686. Date of Electronic Publication: 2026 Jul 14.
Τύπος έκδοσης:	Journal Article
Γλώσσα:	English
Στοιχεία περιοδικού:	Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0151115 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1881-1469 (Electronic) Linking ISSN: 00218820 NLM ISO Abbreviation: J Antibiot (Tokyo) Subsets: MEDLINE
Imprint Name(s):	Publication: 2009- : London : Nature Publishing Group Original Publication: Tokyo, Japan Antibiotics Research Assn.
Ιατρικοί όροι (MeSH):	Ubiquitin-Specific Proteases/metabolism , Ubiquitin-Specific Proteases/chemistry , Deubiquitinating Enzymes/antagonists & inhibitors , Deubiquitinating Enzymes/metabolism , Pyrones*/pharmacology, Proteasome Endopeptidase Complex/metabolism ; Humans ; Mass Spectrometry
Περίληψη:	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. (© 2026. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)
Competing Interests:	Compliance with ethical standards. Conflict of interest: The authors declare no competing interests.
References:	Cell. 2006 Mar 24;124(6):1197-208. (PMID: 16564012) Pharmacol Res. 2020 Jul;157:104557. (PMID: 31756387) Oncogene. 2022 Jul;41(29):3665-3679. (PMID: 35705735) Annu Rev Biochem. 2018 Jun 20;87:697-724. (PMID: 29652515) Exp Mol Med. 2004 Feb 29;36(1):1-12. (PMID: 15031665) Chem Biol. 2011 Nov 23;18(11):1401-12. (PMID: 22118674) FEBS J. 2017 May;284(10):1540-1554. (PMID: 28107776) J Med Chem. 2017 Feb 9;60(3):839-885. (PMID: 27996267) Mol Cell Probes. 2024 Feb;73:101944. (PMID: 38049041) Nat Prod Rep. 2014 Oct;31(10):1425-48. (PMID: 25122538) Signal Transduct Target Ther. 2020 Feb 29;5(1):11. (PMID: 32296023) Mol Cell. 2010 Apr 9;38(1):101-13. (PMID: 20385093) Biomolecules. 2024 Jun 12;14(6):. (PMID: 38927085) Mol Cell. 2025 Jan 16;85(2):323-346. (PMID: 39824171) J Clin Invest. 2022 Sep 15;132(18):. (PMID: 36106637) J Chem Inf Model. 2021 Aug 23;61(8):3891-3898. (PMID: 34278794) Cell Death Dis. 2017 Sep 21;8(9):e3058. (PMID: 28933784) Mol Cell. 2017 Jun 15;66(6):772-779. (PMID: 28622522) Pharmacol Rev. 2019 Apr;71(2):170-197. (PMID: 30867233) Int J Cancer. 2016 Mar 1;138(5):1058-66. (PMID: 25784597) Genes Dis. 2023 Mar 30;11(1):234-251. (PMID: 37588219) Chem Biol. 2002 Oct;9(10):1149-59. (PMID: 12401499) Mol Biomed. 2021 Jul 30;2(1):23. (PMID: 35006464) Mol Cell. 2022 Jan 6;82(1):15-29. (PMID: 34813758) Mol Med Rep. 2026 Mar;33(3):. (PMID: 41543162) Nat Rev Mol Cell Biol. 2023 Apr;24(4):273-287. (PMID: 36284179) Nat Prod Res. 2022 Feb;36(3):760-764. (PMID: 32762459) J Comput Chem. 2010 Jan 30;31(2):455-61. (PMID: 19499576) Nat Commun. 2022 Dec 17;13(1):7799. (PMID: 36528652) Nat Rev Nephrol. 2022 Sep;18(9):573-587. (PMID: 35726016) Front Pharmacol. 2022 Nov 02;13:1033003. (PMID: 36408214) J Biol Chem. 2014 Feb 14;289(7):3876-87. (PMID: 24398693) Mol Cancer. 2020 Oct 1;19(1):146. (PMID: 33004065) MedComm (2020). 2024 Dec 13;5(12):e70036. (PMID: 39678489) Biochemistry. 2009 Mar 24;48(11):2538-49. (PMID: 19182904) J Clin Invest. 2022 Jun 1;132(11):. (PMID: 35642641) Eur J Pharmacol. 2024 Aug 15;977:176747. (PMID: 38880218) Aging (Albany NY). 2019 Nov 13;11(21):9778-9793. (PMID: 31727867) Clin Med Insights Oncol. 2024 Oct 9;18:11795549241281932. (PMID: 39391229) J Biol Chem. 2021 Sep;297(3):101077. (PMID: 34391779) Genes Dis. 2023 Aug 06;11(4):101070. (PMID: 38523673) Chembiochem. 2011 Jan 3;12(1):148-54. (PMID: 21181846) Nat Rev Mol Cell Biol. 2019 Jun;20(6):338-352. (PMID: 30733604) Nat Rev Drug Discov. 2024 Mar;23(3):175-200. (PMID: 38123660) Biomolecules. 2025 Nov 19;15(11):. (PMID: 41301544)
Grant Information:	19H02885 MEXT \| Japan Society for the Promotion of Science (JSPS)
Substance Nomenclature:	EC 3.4.19.12 (Ubiquitin-Specific Proteases) EC 3.4.19.12 (Deubiquitinating Enzymes) 0 (Pyrones) EC 3.4.25.1 (Proteasome Endopeptidase Complex)
Entry Date(s):	Date Created: 20260714 Date Completed: 20260927 Latest Revision: 20261008
Update Code:	20261008
DOI:	10.1038/s41429-026-00948-6
PMID:	42449145
Βάση Δεδομένων:	MEDLINE

Περιγραφή
ISSN:	1881-1469
DOI:	10.1038/s41429-026-00948-6