Aug, 2002
Identification of Saccharomyces cerevisiae isoleucyl-tRNA synthetase as a target of the G(1)-specific inhibitor reveromycin A
JOURNAL OF BIOLOGICAL CHEMISTRY
- Volume
- 277
- Number
- 32
- First page
- 28810
- Last page
- 28814
- Language
- English
- Publishing type
- DOI
- 10.1074/jbc.M203827200
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
To dissect the action mechanism of reveromycin A (RM-A), a G(1)-specific inhibitor, a Saccharomyces cerevisiae dominant mutant specifically resistant to RM-A, was isolated from a strain in which the genes implicated in nonspecific multidrug resistance had been deleted. The mutant gene (YRR2-1) responsible for the resistance was identified as an allele of the ILS1 gene encoding tRNA(Ile) synthetase (MeRS). The activity of HeRS, but not several other aminoacyl-tRNA synthetases examined in wild type cell extract, was highly sensitive to RM-A (IC50 = 8 ng/ml). The IleRS activity of the YRR2-1 mutant was 4-fold more resistant to the inhibitor compared with that of wild type. The mutation IleRS(N660D), near the KMSKS consensus sequence commonly found in the class I aminoacyl transferases, was found to be responsible for RM-A resistance. Moreover, overexpression of the ILS1 gene from a high-copy plasmid conferred RM-A resistance. These results indicated that IleRS is a target of RM-A in vivo. A defect of the GCN2 gene led to decreased RM-A resistance. IleRS inhibition by RM-A led to transcriptional activation of the ILS1 gene via the Gcn2-Gcn4 general amino acid control pathway, and this autoregulation seemed to contribute to RM-A resistance.
- Link information
-
- DOI
- https://doi.org/10.1074/jbc.M203827200
- CiNii Articles
- http://ci.nii.ac.jp/naid/80015523605
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/12050165
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000177342600061&DestApp=WOS_CPL
- ID information
-
- DOI : 10.1074/jbc.M203827200
- ISSN : 0021-9258
- CiNii Articles ID : 80015523605
- Pubmed ID : 12050165
- Web of Science ID : WOS:000177342600061