PY motifs of Rod1 are required for binding to Rsp5 and for drug resistance.
In Saccharomyces cerevisiae, the overexpression of ROD1 confers resistance to o-dinitrobenzene (o-DNB), a representative of target drugs of glutathione S-transferase. The roles of Rod1 in drug resistance have remained to be determined. We isolated the rog3 mutation as a suppressor mutation of the temperature sensitivity of the strain, in that two of the total four glycogen synthase kinase 3 homologs were deleted. Rog3 is homologous to Rod1, and its overexpression also conferred resistance to o-DNB. Furthermore, these two proteins have PY-motifs, and bound to Rsp5, a hect-type ubiquitin ligase. The rsp5-101 mutant showed sensitivity to o-DNB as did the rod1 mutant, a mutant Rod1 containing altered PY motifs was defective in ability to bind to Rsp5 and in conferring o-DNB resistance. These results suggest that interaction of Rod1 and Rsp5 is important for drug resistance.
Andoh
Tomoko
T
Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8551, Hiroshima, Japan. andoh@sci.kumamoto-u.ac.jp
Hirata
Yuzoh
Y
Kikuchi
Akira
A
D020816:Amino Acid Motifs / Q000502:physiology; D004136:Dinitrobenzenes / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011233:Precipitin Tests; D011485:Protein Binding / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013696:Temperature; D043743:Ubiquitin-Protein Ligase Complexes
D004136:Dinitrobenzenes; D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; D008565:Membrane Proteins; C099318:ROD1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C040234:1,2-dinitrobenzene; D043743:Ubiquitin-Protein Ligase Complexes; C469287:RSP5 protein, S cerevisiae