title: Adriamycin inhibits human RH II/Gu RNA helicase activity by binding to its substrate.
abstract: RNA helicases are enzymes important in RNA synthesis, processing, transport, and turnover. Human nucleolar RNA helicase II/Gu protein (RH II/Gu) was expressed in a baculovirus system. The purified recombinant RH II/Gu protein has RNA helicase activity on a 5' tailed ds RNA substrate in vitro. We found that Adriamycin, a widely used anticancer drug, inhibited RH II/Gu helicase activity in a dose-dependent manner with an IC(50) of 40 microM. Adriamycin bound to the RNA substrate, and the binding was disrupted by boiling or treatment with 1% SDS, suggesting that the binding of Adriamycin to RNA is reversible. Adriamycin was also found by gel electrophoresis to bind to yeast tRNA to form slow-migrating complexes. These results suggest that Adriamycin can inhibit RNA synthesis or processing by binding to RNA substrates.
authors.affiliation: Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
authors.forename: K
authors.initials: K
authors.lastname: Zhu
authors.forename: D
authors.initials: D
authors.lastname: Henning
authors.forename: T
authors.initials: T
authors.lastname: Iwakuma
authors.forename: B C
authors.initials: BC
authors.lastname: Valdez
authors.forename: H
authors.initials: H
authors.lastname: Busch
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D050828:Protein Inhibitors of Activated STAT; D012313:RNA / Q000378:metabolism; D020365:RNA Helicases / Q000037:antagonists & inhibitors*; D012343:RNA, Transfer / Q000378:metabolism; D011994:Recombinant Proteins; D025841:Small Ubiquitin-Related Modifier Proteins
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; C106529:PIAS1 protein, human; D050828:Protein Inhibitors of Activated STAT; D011994:Recombinant Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D012313:RNA; D004317:Doxorubicin; D012343:RNA, Transfer; D020365:RNA Helicases