Leptomycin B targets a regulatory cascade of crm1, a fission yeast nuclear protein, involved in control of higher order chromosome structure and gene expression - PubMed

Affiliations

• PMID: 8119981

Free article

Leptomycin B targets a regulatory cascade of crm1, a fission yeast nuclear protein, involved in control of higher order chromosome structure and gene expression

K Nishi et al. J Biol Chem. 1994.

Free article

Abstract

The molecular action of leptomycin B (LMB), an agent inducing arrest of the eukaryotic cell cycle at G1 and G2 phases, was investigated by analyzing an LMB resistance gene of Schizosaccharomyces pombe. A genomic library of an LMB-resistant mutant was screened for LMB resistance, and a DNA fragment containing an open reading frame (ORF) of 1078 amino acids was cloned on a multicopy vector. The plasmid was found to confer drug resistance specifically to LMB. Nucleotide sequencing revealed that the ORF was a mutant gene for the essential nuclear protein crm1, which had been reported to complement a cold-sensitive mutation causing deformed nuclear morphology. The gene product named crm1-N1 had two amino acid replacements (Gly-503 to Asp and Met-546 to Ile). Two allelic mutants of crm1 (crm1-809 and crm1-119) were found to be hypersensitive and resistant, respectively, to LMB. Nuclear morphology of the cold-sensitive crm1-809 mutant at the restrictive temperature was almost the same as that of the wild-type cells treated with LMB. Furthermore, a low concentration of LMB induced the intracellular accumulation of a 25-kDa protein in the wild-type cells, which was immunologically identical to the protein accumulating in the crm1-809 mutant cells. These results strongly suggest that LMB primarily inhibits the function of the crm1 gene which is required for maintaining higher order chromosome structures, correct gene expression, and cell growth in the fission yeast.

Similar articles

• Leptomycin B inactivates CRM1/exportin 1 by covalent modification at a cysteine residue in the central conserved region.

  Kudo N, Matsumori N, Taoka H, Fujiwara D, Schreiner EP, Wolff B, Yoshida M, Horinouchi S. Kudo N, et al. Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9112-7. doi: 10.1073/pnas.96.16.9112. Proc Natl Acad Sci U S A. 1999. PMID: 10430904 Free PMC article.

• Caffeine-resistance in fission yeast is caused by mutations in a single essential gene, crm1+.

  Kumada K, Yanagida M, Toda T. Kumada K, et al. Mol Gen Genet. 1996 Jan 15;250(1):59-68. doi: 10.1007/BF02191825. Mol Gen Genet. 1996. PMID: 8569688

• Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM1.

  Kudo N, Wolff B, Sekimoto T, Schreiner EP, Yoneda Y, Yanagida M, Horinouchi S, Yoshida M. Kudo N, et al. Exp Cell Res. 1998 Aug 1;242(2):540-7. doi: 10.1006/excr.1998.4136. Exp Cell Res. 1998. PMID: 9683540

• Nucleo-cytoplasmic transport of proteins as a target for therapeutic drugs.

  Yashiroda Y, Yoshida M. Yashiroda Y, et al. Curr Med Chem. 2003 May;10(9):741-8. doi: 10.2174/0929867033457791. Curr Med Chem. 2003. PMID: 12678777 Review.

• Trichostatin and leptomycin. Inhibition of histone deacetylation and signal-dependent nuclear export.

  Yoshida M, Horinouchi S. Yoshida M, et al. Ann N Y Acad Sci. 1999;886:23-36. doi: 10.1111/j.1749-6632.1999.tb09397.x. Ann N Y Acad Sci. 1999. PMID: 10667200 Review.

Cited by

• Comprehensive predictions of target proteins based on protein-chemical interaction using virtual screening and experimental verifications.

  Kobayashi H, Harada H, Nakamura M, Futamura Y, Ito A, Yoshida M, Iemura SI, Shin-Ya K, Doi T, Takahashi T, Natsume T, Imoto M, Sakakibara Y. Kobayashi H, et al. BMC Chem Biol. 2012 Apr 5;12:2. doi: 10.1186/1472-6769-12-2. BMC Chem Biol. 2012. PMID: 22480302 Free PMC article.

• A chemical genomic study identifying diversity in cell migration signaling in cancer cells.

  Magi S, Tashiro E, Imoto M. Magi S, et al. Sci Rep. 2012;2:823. doi: 10.1038/srep00823. Epub 2012 Nov 8. Sci Rep. 2012. PMID: 23139868 Free PMC article.

• CDK phosphorylation of a novel NLS-NES module distributed between two subunits of the Mcm2-7 complex prevents chromosomal rereplication.

  Liku ME, Nguyen VQ, Rosales AW, Irie K, Li JJ. Liku ME, et al. Mol Biol Cell. 2005 Oct;16(10):5026-39. doi: 10.1091/mbc.e05-05-0412. Epub 2005 Aug 10. Mol Biol Cell. 2005. PMID: 16093348 Free PMC article.

• The Drosophila embargoed gene is required for larval progression and encodes the functional homolog of schizosaccharomyces Crm1.

  Collier S, Chan HY, Toda T, McKimmie C, Johnson G, Adler PN, O'Kane C, Ashburner M. Collier S, et al. Genetics. 2000 Aug;155(4):1799-807. doi: 10.1093/genetics/155.4.1799. Genetics. 2000. PMID: 10924475 Free PMC article.

• Crm1-mediated nuclear export of the Schizosaccharomyces pombe transcription factor Cuf1 during a shift from low to high copper concentrations.

  Beaudoin J, Labbé S. Beaudoin J, et al. Eukaryot Cell. 2007 May;6(5):764-75. doi: 10.1128/EC.00002-07. Epub 2007 Mar 23. Eukaryot Cell. 2007. PMID: 17384198 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • PomBase, University of Cambridge
  • Saccharomyces Genome Database

• Miscellaneous

  • NCI CPTAC Assay Portal