Document Detail


Rapamycin specifically interferes with the developmental response of fission yeast to starvation.
MedLine Citation:
PMID:  9335279     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Rapamycin is a microbial macrolide which belongs to a family of immunosuppressive drugs that suppress the immune system by blocking stages of signal transduction in T lymphocytes. In Saccharomyces cerevisiae cells, as in T lymphocytes, rapamycin inhibits growth and cells become arrested at the G1 stage of the cell cycle. Rapamycin is also an effective antifungal agent, affecting the growth of yeast and filamentous fungi. Unexpectedly, we observed that rapamycin has no apparent effect on the vegetative growth of Schizosaccharomyces pombe. Instead, the drug becomes effective only when cells experience starvation. Under such conditions, homothallic wild-type cells will normally mate and undergo sporulation. In the presence of rapamycin, this sexual development process is strongly inhibited and cells adopt an alternative physiological option and enter stationary phase. Rapamycin strongly inhibits sexual development of haploid cells prior to the stage of sexual conjugation. In contrast, the drug has only a slight inhibitory effect on the sporulation of diploid cells. A genetic approach was applied to identify the signal transduction pathway that is inhibited by rapamycin. The results indicate that either rapamycin did not suppress the derepression of sexual development of strains in which adenylate cyclase was deleted or the cyclic AMP-dependent protein kinase encoded by pka1 was mutated. Nor did rapamycin inhibit the unscheduled meiosis observed in pat1-114 mutants. Overexpression of ras1+, an essential gene for sexual development, did not rescue the sterility of rapamycin-treated cells. However, expression of the activated allele, ras1Val17, antagonized the effect of rapamycin and restored the ability of the cells to respond to mating signals in the presence of the drug. We discuss possible mechanisms for the inhibitory effect of rapamycin on sexual development in S. pombe.
Authors:
R Weisman; M Choder; Y Koltin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of bacteriology     Volume:  179     ISSN:  0021-9193     ISO Abbreviation:  J. Bacteriol.     Publication Date:  1997 Oct 
Date Detail:
Created Date:  1997-11-04     Completed Date:  1997-11-04     Revised Date:  2010-09-13    
Medline Journal Info:
Nlm Unique ID:  2985120R     Medline TA:  J Bacteriol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  6325-34     Citation Subset:  IM    
Affiliation:
Department of Molecular Microbiology and Biotechnology, Faculty of Life Sciences, Tel Aviv University, Israel. ronitt@post.tau.ac.il
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / metabolism
Alleles
Antifungal Agents / pharmacology*
Conjugation, Genetic / drug effects
Cyclic AMP / metabolism
Cyclic AMP-Dependent Protein Kinases / genetics,  metabolism
Fungal Proteins / genetics,  physiology
Genes, Fungal
Interphase / drug effects
Meiosis
Phenotype
Polyenes / pharmacology*
Saccharomyces cerevisiae Proteins*
Schizosaccharomyces / drug effects*,  genetics,  growth & development,  physiology
Schizosaccharomyces pombe Proteins*
Sirolimus
Spores, Fungal / drug effects,  physiology
ras Proteins / genetics,  physiology
Chemical
Reg. No./Substance:
0/Antifungal Agents; 0/Fungal Proteins; 0/Polyenes; 0/Saccharomyces cerevisiae Proteins; 0/Schizosaccharomyces pombe Proteins; 53123-88-9/Sirolimus; 60-92-4/Cyclic AMP; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 3.6.5.2/RAS1 protein, S cerevisiae; EC 3.6.5.2/Ras1 protein, S pombe; EC 3.6.5.2/ras Proteins; EC 4.6.1.1/Adenylate Cyclase
Comments/Corrections

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