A K-252a-resistance gene, sks1+, encodes a protein similar to the Caenorhabditis elegans F37 A4.5 gene product and confers multidrug resistance in Schizosaccharomyces pombe.
A gene named sks1+ was cloned as a suppressor of the K-252a-sensitivity phenotype of Schizosaccharomyces pombe (Sp) from a gene library of the parental Sp chromosomal DNA constructed with a multicopy vector pDB248'. The gene encoded a 308-amino-acid (aa) protein similar to the Caenorhabditis elegans F37 A4.5 gene product and to the mouse and Drosophila Mov34 gene products. The sks1+ null mutants obtained by gene disruption were non-viable, indicating that sks1+ is essential for vegetative growth. The parental Sp strain carrying multiple copies of sks1+ showed distinct cross-resistance to staurosporine, thiabendazole and vanadate in addition to K-252a, although Sks1 has no similarity in aa sequence to those of ATP-binding cassette (ABC)-type transporters. The multicopy plasmid containing sks1+ conferred multidrug resistance (MDR), even in a mutant cell defective in pmd1+ encoding an ABC-type transporter. It is therefore unlikely that the function of pmd1+ is involved in MDR conferred by sks1+. These results suggest that sks1+ is a functionally novel MDR gene.
Usui
T
T
Department of Biotechnology, University of Tokyo, Japan.
Yoshida
M
M
Honda
A
A
Beppu
T
T
Horinouchi
S
S
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D002227:Carbazoles / Q000494:pharmacology*; D003001:Cloning, Molecular; D018432:Drug Resistance, Multiple / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D026121:Indole Alkaloids; D008969:Molecular Sequence Data; D012568:Schizosaccharomyces / Q000187:drug effects / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; C049985:staurosporine aglycone