title: Selective chemical intervention in the proteome of Caenorhabditis elegans.
abstract: We present the first study of protein regulation by ligands in Caenorhabditis elegans. The ligands were peptidyl-prolyl isomerase inhibitors of cyclophilins. Up-regulation is observed for several heat shock proteins and one ligand in particular caused a greater than 2-fold enhancement of cyclophilin CYN-5. Additionally, several metabolic enzymes display elevated levels. This approach, using label-free relative quantification, provides an extremely attractive way of measuring the effect of ligands on an entire proteome, with minimal sample pretreatment, which could be applicable to large-scale studies. In this initial study, which compares the effect of three ligands, 54 unique proteins have been identified that are up- (51) or down- (3) regulated in the presence of a given ligand. A total of 431 C. elegans proteins were identified. Our methodology provides an intriguing new direction for in vivo screening of the effects of novel and untested ligands at the whole organism level.
authors.affiliation: Centre for Translational and Chemical Biology, University of Edinburgh, Edinburgh EH9 3JJ, UK.
authors.forename: Holger
authors.initials: H
authors.lastname: Husi
authors.forename: Fiona
authors.initials: F
authors.lastname: McAllister
authors.forename: Nicos
authors.initials: N
authors.lastname: Angelopoulos
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Butler
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Bailey
authors.forename: Kirk
authors.initials: K
authors.lastname: Malone
authors.forename: Logan
authors.initials: L
authors.lastname: Mackay
authors.forename: Paul
authors.initials: P
authors.lastname: Taylor
authors.forename: Antony P
authors.initials: AP
authors.lastname: Page
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Turner
authors.forename: Perdita E
authors.initials: PE
authors.lastname: Barran
authors.forename: Malcolm
authors.initials: M
authors.lastname: Walkinshaw
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D021983:Cyclophilins / Q000187:drug effects* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D008024:Ligands; D019696:Peptidylprolyl Isomerase / Q000494:pharmacology; D020543:Proteome / Q000187:drug effects*
chemical_list: D029742:Caenorhabditis elegans Proteins; D008024:Ligands; D020543:Proteome; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase