CHARACTERIZATION OF A NOVEL SCHIZOSACCHAROMYCES-POMBE MULTIDRUG-RESISTANCE TRANSPORTER CONFERRING BREFELDIN-A RESISTANCE

Brefeldin A disrupts protein secretion and causes the redistribution o f the Golgi complex to endoplasmic reticulum in both mammalian cells a nd wild type Schizosaccharomyces pombe. We have previously isolated si x different genes that, when present in multiple copies, confer brefel din A resistance to wild type S. pombe. Here we present the characteri zation of one of these genes, hba2, which encodes a novel S. pombe pro tein that shares significant sequence similarity to members of the ATP -binding cassette superfamily of transport proteins. Examination of hb a2 expression determined that this gene is overexpressed in mutant str ains resistant to brefeldin A due to mutations in the negative regulat or crm1(bar1) gene or the bar2 gene. The increase of hba2 expression w as independent of the pap1 transcription factor which is repressed by wild type crm1. These results suggest that crm1 negatively regulates m ultiple transcription factors including one that modulates hba2 transc ription. (C) 1995 Academic Press, Inc.