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Genetic selection of peptide inhibitors of biological pathways.
- Source :
-
Science (New York, N.Y.) [Science] 1999 Jul 23; Vol. 285 (5427), pp. 591-5. - Publication Year :
- 1999
-
Abstract
- Genetic selections were used to find peptides that inhibit biological pathways in budding yeast. The peptides were presented inside cells as peptamers, surface loops on a highly expressed and biologically inert carrier protein, a catalytically inactive derivative of staphylococcal nuclease. Peptamers that inhibited the pheromone signaling pathway, transcriptional silencing, and the spindle checkpoint were isolated. Putative targets for the inhibitors were identified by a combination of two-hybrid analysis and genetic dissection of the target pathways. This analysis identified Ydr517w as a component of the spindle checkpoint and reinforced earlier indications that Ste50 has both positive and negative roles in pheromone signaling. Analysis of transcript arrays showed that the peptamers were highly specific in their effects, which suggests that they may be useful reagents in organisms that lack sophisticated genetics as well as for identifying components of existing biological pathways that are potential targets for drug discovery.
- Subjects :
- Amino Acid Sequence
Calcium-Calmodulin-Dependent Protein Kinases metabolism
Fungal Proteins metabolism
G1 Phase
Galactose metabolism
Lipoproteins metabolism
Mating Factor
Micrococcal Nuclease
Mitosis
Molecular Sequence Data
Peptide Library
Peptides genetics
Peptides metabolism
Protein Binding
Protein Serine-Threonine Kinases
Protein-Tyrosine Kinases
Saccharomyces cerevisiae cytology
Saccharomyces cerevisiae genetics
Spindle Apparatus drug effects
Transcription, Genetic
Peptides pharmacology
Pheromones metabolism
Saccharomyces cerevisiae metabolism
Saccharomyces cerevisiae Proteins
Selection, Genetic
Signal Transduction
Spindle Apparatus metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0036-8075
- Volume :
- 285
- Issue :
- 5427
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 10417390
- Full Text :
- https://doi.org/10.1126/science.285.5427.591