Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases

• Verfasst von: Lauinger, Linda [VerfasserIn]
• Verfasst von: Shostak, Anton [VerfasserIn]
• Verfasst von: Cemel, Ibrahim [VerfasserIn]
• Verfasst von: Ha, Nati [VerfasserIn]
• Verfasst von: Stankovic-Valentin, Nicolas [VerfasserIn]
• Verfasst von: Melchior, Frauke [VerfasserIn]
• Verfasst von: Brunner, Michael [VerfasserIn]
• Verfasst von: Diernfellner, Axel [VerfasserIn]
• Titel: Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases
• Verf.angabe: Linda Lauinger, Jing Li, Anton Shostak, Ibrahim Avi Cemel, Nati Ha, Yaru Zhang, Philipp E. Merkl, Simon Obermeyer, Nicolas Stankovic-Valentin, Tobias Schafmeier, Walter J. Wever, Albert A. Bowers, Kyle P. Carter, Amy E. Palmer, Herbert Tschochner, Frauke Melchior, Raymond J. Deshaies, Michael Brunner & Axel Diernfellner
• E-Jahr: 2017
• Jahr: 01 May 2017
• Umfang: 6 S.
• Fussnoten: Gesehen am 25.09.2018
• Titel Quelle: Enthalten in: Nature chemical biology
• Ort Quelle: Basingstoke : Nature Publishing Group, 2005
• Jahr Quelle: 2017
• Band/Heft Quelle: 13(2017), 7, Seite 709-714
• ISSN Quelle: 1552-4469
• DOI: doi:10.1038/nchembio.2370
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1581259107

Abstract

Thiolutin is a disulfide-containing antibiotic and anti-angiogenic compound produced by Streptomyces. Its biological targets are not known. We show that reduced thiolutin is a zinc chelator that inhibits the JAB1/MPN/Mov34 (JAMM) domain-containing metalloprotease Rpn11, a deubiquitinating enzyme of the 19S proteasome. Thiolutin also inhibits the JAMM metalloproteases Csn5, the deneddylase of the COP9 signalosome; AMSH, which regulates ubiquitin-dependent sorting of cell-surface receptors; and BRCC36, a K63-specific deubiquitinase of the BRCC36-containing isopeptidase complex and the BRCA1-BRCA2-containing complex. We provide evidence that other dithiolopyrrolones also function as inhibitors of JAMM metalloproteases.