PMID: 11318103Apr 25, 2001Paper

Sequence of Crm1/exportin 1 mutant alleles reveals critical sites associated with multidrug resistance

Current Genetics
S CarobbioV Spataro

Abstract

We have previously shown that genes involved in a novel pathway of multidrug resistance (MDR) in the fission yeast Schizosaccharomyces pombe are functionally conserved in human cells (V. Spataro et al. (1997) J Biol Chem 272: 30470-30475). The human homologue of one of these genes, hCRM1, has recently been identified and found to function in nucleocytoplasmic export, a process which controls the subcellular localization and hence activity of a number of key cell cycle regulators and transcription factors. Several mutant alleles of crm1 confer a phenotype of MDR in S. pombe, through the nuclear accumulation of the AP-1 transcription factor Pap1. We therefore sequenced mutations of crm1 in fission yeast in order to guide the search for analogous hCRM1 mutations which could play a role in tumour-drug resistance. Fifteen yeast crm1 mutants were assessed by PCR and DNA sequencing. Four mis-sense mutations were identified in the open reading frame, three of which (G to A transitions at nucleotide positions 385, 895 and 1,288) were capable of conferring the MDR phenotype alone. For three of the four mutations found, the corresponding amino acid changes affect residues which are conserved in the human homologue hCRM1 and lie in highly ...Continue Reading

Citations

Jun 15, 2018·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Takahide HibiHirofumi Aiba

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