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Proc Natl Acad Sci U S A

Title:		Transdominant genetic analysis of a growth control pathway
Author(s):		Caponigro G; Abedi MR; Hurlburt AP; Maxfield A; Judd W; Kamb A;
Address:		"Ventana Genetics, Inc., 421 Wakara Way, Salt Lake City, UT 84108, USA"
Journal Title:		Proc Natl Acad Sci U S A
Year:		1998
Volume:		95
Issue:		13
Page Number:		7508 - 7513
DOI:		10.1073/pnas.95.13.7508
ISSN/ISBN:		0027-8424 (Print) 1091-6490 (Electronic) 0027-8424 (Linking)
Abstract:		"Genetic selections that use proteinaceous transdominant inhibitors encoded by DNA libraries to cause mutant phenocopies may facilitate genetic analysis in traditionally nongenetic organisms. We performed a selection for random short peptides and larger protein fragments (collectively termed 'perturbagens') that inhibit the yeast pheromone response pathway. Peptide and protein fragment perturbagens that permit cell division in the presence of pheromone were recovered. Two perturbagens were derived from proteins required for pheromone response, and an additional two were derived from proteins that may negatively influence the pheromone response pathway. Furthermore, three known components of the pathway were identified as probable perturbagen targets based on physical interaction assays. Thus, by selection for transdominant inhibitors of pheromone response, multiple pathway components were identified either directly as gene fragments or indirectly as the likely targets of specific perturbagens. These results, combined with the results of previous work [Holzmayer, T. A., Pestov, D. G. & Roninson, I. B. (1992) Nucl. Acids. Res. 20, 711-717; Whiteway, M., Dignard, D. & Thomas, D. Y. (1992) Proc. Natl. Acad. Sci. USA 89, 9410-9414; and Gudkov, A. V., Kazarov, A. R., Thimmapaya, R., Axenovich, S. A., Mazo, I. A. & Roninson, I. B. (1994) Proc. Natl. Acad. Sci. USA 91, 3744-3748], suggest that transdominant genetic analysis of the type described here will be broadly applicable"
Keywords:		"Cell Cycle/*genetics Epistasis, Genetic Genes, Dominant Genetic Techniques Mating Factor *Models, Genetic Peptide Fragments/chemistry/isolation & purification/pharmacology Peptide Library Peptides/antagonists & inhibitors/genetics Phenotype Pheromones/gen;"
Notes:		"MedlineCaponigro, G Abedi, M R Hurlburt, A P Maxfield, A Judd, W Kamb, A eng 1998/06/24 Proc Natl Acad Sci U S A. 1998 Jun 23; 95(13):7508-13. doi: 10.1073/pnas.95.13.7508"