title: Leishmania donovani P23 protects parasites against HSP90 inhibitor-mediated growth arrest.
abstract: In Leishmania donovani, the HSP90 chaperone complex plays an essential role in the control of the parasite's life cycle, general viability and infectivity. Several of the associated co-chaperones were also shown to be essential for viability and/or infectivity to mammalian cells. Here, we identify and describe the co-chaperone P23 and distinguish its function from that of the structurally related small heat shock protein HSP23. P23 is expressed constitutively and associates itself with members of the HSP90 complex, i.e. HSP90 and Sti1. Viable P23 gene replacement mutants could be raised and confirmed as null mutants without deleterious effects on viability under a variety of physiological growth conditions. The null mutant also displays near-wild-type infectivity, arguing against a decisive role played by P23 in laboratory settings. However, the P23 null mutant displays a marked hypersensitivity against HSP90 inhibitors geldanamycin and radicicol. P23 also appears to affect the radicicol resistance of a HSP90 Leu33-Ile mutant described previously. Therefore, the annotation of L. donovani P23 as HSP90-interacting co-chaperone is confirmed.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, P.O. Box 30 41 20, 20324, Hamburg, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Hombach
authors.forename: Gabi
authors.initials: G
authors.lastname: Ommen
authors.forename: Victoria
authors.initials: V
authors.lastname: Sattler
authors.forename: Joachim
authors.initials: J
authors.lastname: Clos
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D007893:Leishmania donovani / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity; D008018:Life Cycle Stages / Q000187:drug effects; D018942:Macrolides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D059467:Transcriptome; D014162:Transfection
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D018942:Macrolides; D018832:Molecular Chaperones; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C035359:monorden; C001277:geldanamycin