Abstract
Leptomycin B (LMB) is a Streptomyces metabolite that causes specific inhibition of the cell cycle of yeast and mammalian cells. The target molecule of LMB in fission yeast has been shown by genetic analysis to be CRM1, a highly conserved protein in eukaryotes. We isolated a human homolog of CRM1 (hCRM1) which was expressed ubiquitously in human tissues and showed that hCRM1 was essential for nuclear export of proteins. CRM1 was shown to be a receptor for the nuclear export signal (NES) of proteins in both yeast and mammalian cells. LMB binds directly to CRM1, which resulted in dissociation of the NES from the nuclear export machinery containing CRM1. Thus, LMB serves as a potent tool for understanding the molecular mechanisms of nucleo-cytoplasmic transport of proteins.
