title: Inhibition of proteasome activity by tyropeptin A in PC12 cells.
abstract: Tyropeptin A, a potent proteasome inhibitor not reported before, was produced by Kitasatospora sp. MK993-dF2. In this study, we investigated the effects of tyropeptin A on proteasome activity in PC12 cells. Tyropeptin A inhibited the intracellular proteasome activity in a dose-dependent way and seemed to cause neurite outgrowth. As expected, ubiquitinated proteins that should be substrates for the proteasome accumulated in cells treated with tyropeptin A. Hence, it appears that tyropeptin A can permeate into cells and there inhibit the intracellular proteasome activity.
authors.affiliation: Institute of Microbial Chemistry, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan. imomose@bikaken.or.jp
authors.forename: Isao
authors.initials: I
authors.lastname: Momose
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Sekizawa
authors.forename: Hironobu
authors.initials: H
authors.lastname: Iinuma
authors.forename: Tomio
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D003546:Cysteine Endopeptidases; D004151:Dipeptides / Q000378:metabolism / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D016501:Neurites / Q000187:drug effects; D016716:PC12 Cells; D046988:Proteasome Endopeptidase Complex; D051381:Rats
chemical_list: D000903:Antibiotics, Antineoplastic; D004151:Dipeptides; D009097:Multienzyme Complexes; C449021:tyropeptin A; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex