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Chemical Compound Review

Elactocin     (2E,10E,12E,16E,18E)-17- ethyl-6-hydroxy-3...

Synonyms: Leptomycin B, AC1NUQVG, Probes1_000170, Probes2_000132, NSC-364372, ...
 
 
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Disease relevance of Elactocin

 

High impact information on Elactocin

  • In vitro, CRM1 forms a leptomycin B-sensitive complex involving cooperative binding of both RanGTP and the nuclear export signal (NES) from either the Rev or PKI proteins [6].
  • The activity of this NES is inhibited by the antibiotic Leptomycin B, suggesting that Exd is exported by a CRM1/exportin1-related export pathway [7].
  • In support of this hypothesis, we found that treatment of cells with leptomycin B, which disrupted Cyclin B1-CRM1 interactions, led to a marked nuclear accumulation of Cyclin B1 [8].
  • Analysis of spindles within leptomycin B-treated cells shows that their centromeres were under increased tension [9].
  • In leptomycin B-treated cells, centromeres frequently associated with continuous microtubule bundles that spanned the centromeres, indicating that their kinetochores do not maintain discrete end-on attachments to single kinetochore fibres [9].
 

Chemical compound and disease context of Elactocin

 

Biological context of Elactocin

 

Anatomical context of Elactocin

 

Associations of Elactocin with other chemical compounds

 

Gene context of Elactocin

  • In vertebrates and Schizosaccharomyces pombe, the toxin leptomycin B (LMB) inhibits CRM1-mediated export by interacting directly with CRM1 and disrupting the trimeric Ran-GTP-CRM1-NES export complex [24].
  • Finally, treatment of cells with leptomycin B (a drug that blocks export of U snRNAs to the cytoplasm and consequently import of new snRNPs into the nucleus) is shown to deplete snRNPs (but not SMN or SIP1) from the Cajal body [25].
  • Inhibition of FRAP nuclear export by LMB coincides with diminished p70(s6k) activation and 4E-BP1 phosphorylation [26].
  • Deletion of this NES or treatment with the CRM1-specific inhibitor leptomycin B leads to overall nuclear accumulation of merlin isoforms missing exon 2 [27].
  • We demonstrate that inhibition of CRM1-mediated nuclear export by treatment of cells with leptomycin B results in endogenous Smad4 accumulating very rapidly in the nucleus [28].
 

Analytical, diagnostic and therapeutic context of Elactocin

References

  1. A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking. Stommel, J.M., Marchenko, N.D., Jimenez, G.S., Moll, U.M., Hope, T.J., Wahl, G.M. EMBO J. (1999) [Pubmed]
  2. Cytoplasmic HuR expression correlates with poor outcome and with cyclooxygenase 2 expression in serous ovarian carcinoma. Erkinheimo, T.L., Lassus, H., Sivula, A., Sengupta, S., Furneaux, H., Hla, T., Haglund, C., Butzow, R., Ristimäki, A. Cancer Res. (2003) [Pubmed]
  3. Redefining the subcellular location and transport of APC: new insights using a panel of antibodies. Brocardo, M., Näthke, I.S., Henderson, B.R. EMBO Rep. (2005) [Pubmed]
  4. Nucleo-cytoplasmic transport of proteins as a target for therapeutic drugs. Yashiroda, Y., Yoshida, M. Current medicinal chemistry. (2003) [Pubmed]
  5. Leptomycin B inhibition of signal-mediated nuclear export by direct binding to CRM1. Kudo, N., Wolff, B., Sekimoto, T., Schreiner, E.P., Yoneda, Y., Yanagida, M., Horinouchi, S., Yoshida, M. Exp. Cell Res. (1998) [Pubmed]
  6. CRM1 is an export receptor for leucine-rich nuclear export signals. Fornerod, M., Ohno, M., Yoshida, M., Mattaj, I.W. Cell (1997) [Pubmed]
  7. Control of the nuclear localization of Extradenticle by competing nuclear import and export signals. Abu-Shaar, M., Ryoo, H.D., Mann, R.S. Genes Dev. (1999) [Pubmed]
  8. Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1. Yang, J., Bardes, E.S., Moore, J.D., Brennan, J., Powers, M.A., Kornbluth, S. Genes Dev. (1998) [Pubmed]
  9. Crm1 is a mitotic effector of Ran-GTP in somatic cells. Arnaoutov, A., Azuma, Y., Ribbeck, K., Joseph, J., Boyarchuk, Y., Karpova, T., McNally, J., Dasso, M. Nat. Cell Biol. (2005) [Pubmed]
  10. Comparison of viral genomic RNA sorting mechanisms in human immunodeficiency virus type 1 (HIV-1), HIV-2, and Moloney murine leukemia virus. Dorman, N., Lever, A. J. Virol. (2000) [Pubmed]
  11. ICP27-dependent resistance of herpes simplex virus type 1 to leptomycin B is associated with enhanced nuclear localization of ICP4 and ICP0. Lengyel, J., Strain, A.K., Perkins, K.D., Rice, S.A. Virology (2006) [Pubmed]
  12. p53 is associated with cellular microtubules and is transported to the nucleus by dynein. Giannakakou, P., Sackett, D.L., Ward, Y., Webster, K.R., Blagosklonny, M.V., Fojo, T. Nat. Cell Biol. (2000) [Pubmed]
  13. Leptomycin B-sensitive nuclear export of MAPKAP kinase 2 is regulated by phosphorylation. Engel, K., Kotlyarov, A., Gaestel, M. EMBO J. (1998) [Pubmed]
  14. A novel transferable nuclear export signal mediates CRM1-independent nucleocytoplasmic shuttling of the human cytomegalovirus transactivator protein pUL69. Lischka, P., Rosorius, O., Trommer, E., Stamminger, T. EMBO J. (2001) [Pubmed]
  15. A nuclear export signal within the high mobility group domain regulates the nucleocytoplasmic translocation of SOX9 during sexual determination. Gasca, S., Canizares, J., De Santa Barbara, P., Mejean, C., Poulat, F., Berta, P., Boizet-Bonhoure, B. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  16. Adapter protein SH2-B beta undergoes nucleocytoplasmic shuttling: implications for nerve growth factor induction of neuronal differentiation. Chen, L., Carter-Su, C. Mol. Cell. Biol. (2004) [Pubmed]
  17. MyoD-dependent induction during myoblast differentiation of p204, a protein also inducible by interferon. Liu, C., Wang, H., Zhao, Z., Yu, S., Lu, Y.B., Meyer, J., Chatterjee, G., Deschamps, S., Roe, B.A., Lengyel, P. Mol. Cell. Biol. (2000) [Pubmed]
  18. Facilitated nucleocytoplasmic shuttling of the Ran binding protein RanBP1. Plafker, K., Macara, I.G. Mol. Cell. Biol. (2000) [Pubmed]
  19. Nuclear import and export signals enable rapid nucleocytoplasmic shuttling of the atypical protein kinase C lambda. Perander, M., Bjorkoy, G., Johansen, T. J. Biol. Chem. (2001) [Pubmed]
  20. Nuclear export of actin: a novel mechanism regulating the subcellular localization of a major cytoskeletal protein. Wada, A., Fukuda, M., Mishima, M., Nishida, E. EMBO J. (1998) [Pubmed]
  21. Activation of p53 in cervical carcinoma cells by small molecules. Hietanen, S., Lain, S., Krausz, E., Blattner, C., Lane, D.P. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  22. The net repressor is regulated by nuclear export in response to anisomycin, UV, and heat shock. Ducret, C., Maira, S.M., Dierich, A., Wasylyk, B. Mol. Cell. Biol. (1999) [Pubmed]
  23. CSN5/Jab1 is involved in ligand-dependent degradation of estrogen receptor {alpha} by the proteasome. Calligé, M., Kieffer, I., Richard-Foy, H. Mol. Cell. Biol. (2005) [Pubmed]
  24. The NES-Crm1p export pathway is not a major mRNA export route in Saccharomyces cerevisiae. Neville, M., Rosbash, M. EMBO J. (1999) [Pubmed]
  25. The spinal muscular atrophy disease gene product, SMN: A link between snRNP biogenesis and the Cajal (coiled) body. Carvalho, T., Almeida, F., Calapez, A., Lafarga, M., Berciano, M.T., Carmo-Fonseca, M. J. Cell Biol. (1999) [Pubmed]
  26. Cytoplasmic-nuclear shuttling of FKBP12-rapamycin-associated protein is involved in rapamycin-sensitive signaling and translation initiation. Kim, J.E., Chen, J. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  27. Nucleocytoplasmic transfer of the NF2 tumor suppressor protein merlin is regulated by exon 2 and a CRM1-dependent nuclear export signal in exon 15. Kressel, M., Schmucker, B. Hum. Mol. Genet. (2002) [Pubmed]
  28. Transforming growth factor beta-independent shuttling of Smad4 between the cytoplasm and nucleus. Pierreux, C.E., Nicolás, F.J., Hill, C.S. Mol. Cell. Biol. (2000) [Pubmed]
  29. Identification of multiple nuclear export sequences in Fanconi anemia group A protein that contribute to CRM1-dependent nuclear export. Ferrer, M., Rodríguez, J.A., Spierings, E.A., de Winter, J.P., Giaccone, G., Kruyt, F.A. Hum. Mol. Genet. (2005) [Pubmed]
  30. Activity- and calcineurin-independent nuclear shuttling of NFATc1, but not NFATc3, in adult skeletal muscle fibers. Shen, T., Liu, Y., Cseresnyés, Z., Hawkins, A., Randall, W.R., Schneider, M.F. Mol. Biol. Cell (2006) [Pubmed]
  31. Inhibition of nuclear import of LIMK2 in endothelial cells by protein kinase C-dependent phosphorylation at Ser-283. Goyal, P., Pandey, D., Behring, A., Siess, W. J. Biol. Chem. (2005) [Pubmed]
  32. Nuclear pore localization and nucleocytoplasmic transport of eIF-5A: evidence for direct interaction with the export receptor CRM1. Rosorius, O., Reichart, B., Krätzer, F., Heger, P., Dabauvalle, M.C., Hauber, J. J. Cell. Sci. (1999) [Pubmed]
 
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