title: Development of Small Molecular Proteasome Inhibitors Using a Caenorhabditis elegans Screen.
abstract: We have developed a screening protocol to identify compounds with characteristics of small molecule proteasome inhibitors using the real-time analysis of the Caenorhabditis elegans germ line. This screen is able to identify compounds that induce germ line phenotypes characteristic of a reduction in proteasome function such as changes in polarity, aberrant nuclear morphology, and stimulation of apoptosis. This basic protocol is amenable to a high throughput (96-well) format and has been used successfully to identify multiple compounds for further analysis based on structural elements from the naturally occurring compounds lactacystin and the β-lactone homologs omuralide and salinosporamide A. The further development of this assay system should allow for the generation of novel small molecule proteasome inhibitors in a genetically tractable whole animal amenable to biochemical analysis.
authors.affiliation: Department of Biology, The College of New Jersey, 2000 Pennington Road, Ewing, NJ 08628, USA.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Nayak
authors.affiliation: Department of Biology, The College of New Jersey, 2000 Pennington Road, Ewing, NJ 08628, USA.
authors.forename: Michela
authors.initials: M
authors.lastname: Fiaschi
authors.affiliation: Department of Biology, The College of New Jersey, 2000 Pennington Road, Ewing, NJ 08628, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: King
authors.affiliation: Department of Chemistry, The College of New Jersey, 2000 Pennington Road, Ewing, NJ 08628, USA.
authors.forename: Erica R
authors.initials: ER
authors.lastname: Tabakin
authors.affiliation: Department of Biology, The College of New Jersey, 2000 Pennington Road, Ewing, NJ 08628, USA ; Department of Chemistry, The College of New Jersey, 2000 Pennington Road, Ewing, NJ 08628, USA.
authors.forename: Lyndsay
authors.initials: L
authors.lastname: Wood
authors.affiliation: Department of Chemistry, The College of New Jersey, 2000 Pennington Road, Ewing, NJ 08628, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hunt