期刊
NATURE CHEMICAL BIOLOGY
卷 13, 期 7, 页码 709-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nchembio.2370
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资金
- Deutsche Forschungsgemeinschaft [Sonderforschungsbereich 1036, Transregio 186, DI1874/1]
- US National Institutes of Health [CA164803]
- Howard Hughes Medical Institute
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.
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