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.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Lauinger L,Li J,Shostak A,Cemel IA,Ha N,Zhang Y,Merkl PE,Obermeyer S,Stankovic-Valentin N,Schafmeier T,Wever WJ,Bowers AA,Carter KP,Palmer AE,Tschochner H,Melchior F,Deshaies RJ,Brunner M,Diernfellner Adoi
10.1038/nchembio.2370subject
Has Abstractpub_date
2017-07-01 00:00:00pages
709-714issue
7eissn
1552-4450issn
1552-4469pii
nchembio.2370journal_volume
13pub_type
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