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Chemical Compound Review

Elactocin     (2E,5S,6R,7S,9R,10E,12E,15R,16 Z,18E)-17...

Synonyms: Mantuamycin, Leptomycin B, CI-940, AC1O5LDH, LS-96801, ...
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Disease relevance of LMB


High impact information on LMB


Biological context of LMB


Anatomical context of LMB

  • This communication demonstrates that LMB treatment of various cell lines led to an increase in the steady-state levels of the p53 protein as a result of an increase in its stability [13].
  • In mitotic cells where CRM1 is in the cytoplasm, adenovirus particles were not associated with microtubules but upon LMB treatment, they enriched at the spindle poles implying that CRM1 inhibited microtubule association of adenovirus [1].
  • Alteration of conserved leucine residues to alanine within Jab1/CSN5-NES abolished the interaction with CRM1 in vitro and impaired LMB-sensitive nuclear export and the ability to induce p27 breakdown in cultured cells [14].
  • By contrast, LmB treatment of v-src-transformed fibroblasts caused endogenous AnxII to accumulate in nuclei [15].
  • In LMB-treated cells, vRNPs were found in a peripheral nuclear location that localized with the nuclear lamina. vRNPs were not colocalized with either M1 or NS2 [16].

Associations of LMB with other chemical compounds

  • Moreover, we show that expression of the NES-disrupted cyclin B1 or LMB treatment of the cells is able to override the DNA damage-induced G2 checkpoint when combined with caffeine treatment [9].
  • Using purified recombinant factors, we show by co-precipitation, gel mobility shift and protein footprinting assays that full-length Rev protein interacts directly with CRM1 in vitro independently of both the integrity of the characteristic leucine residues of the NES and the presence of the cytotoxin leptomycin B (LMB) [17].
  • Dioxin treatment caused a more rapid accumulation of AhR in the nucleus than LMB treatment [18].

Gene context of LMB

  • It is predicted that LMB should inhibit nuclear-cytoplasmic shuttling by MDM2 and subsequently stabilize p53 [13].
  • Further, we demonstrated that Abi-1 shuttles in and out of the nucleus in a leptomycin B (LMB)-dependent manner and that complete nuclear translocation of Abi-1 in the absence of LMB requires the combined inactivation of the SNARE, WAB, and SH3 domains of Abi-1 [19].
  • Nuclear-cytoplasmic translocation plays an important role because leptomycin B (LMB), a chemical inhibitor of CRM1-dependent nuclear export, prevents p27 degradation mediated by Jab1/CSN5 [14].
  • Besides the tetradecapeptide repeat domain, human HDAC6 possesses two LMB-sensitive nuclear export signals and a nuclear localization signal [20].
  • Indeed, we observed that nuclear export of human NMD3 (hNMD3) is sensitive to leptomycin B (LMB), which inactivates CRM1 [21].

Analytical, diagnostic and therapeutic context of LMB

  • In situ hybridization experiments performed with a Texas red-coupled oligo(dT) probe revealed that LMB produced a partial short-term accumulation of a poly(A)+RNA subset in the nucleus [22].


  1. Nuclear targeting of adenovirus type 2 requires CRM1-mediated nuclear export. Strunze, S., Trotman, L.C., Boucke, K., Greber, U.F. Mol. Biol. Cell (2005) [Pubmed]
  2. Ratjadones inhibit nuclear export by blocking CRM1/exportin 1. Köster, M., Lykke-Andersen, S., Elnakady, Y.A., Gerth, K., Washausen, P., Höfle, G., Sasse, F., Kjems, J., Hauser, H. Exp. Cell Res. (2003) [Pubmed]
  3. Nuclear interactions are necessary for translational enhancement by spleen necrosis virus RU5. Dangel, A.W., Hull, S., Roberts, T.M., Boris-Lawrie, K. J. Virol. (2002) [Pubmed]
  4. In vivo and in vitro anticancer activity of the structurally novel and highly potent antibiotic CI-940 and its hydroxy analog (PD 114,721). Roberts, B.J., Hamelehle, K.L., Sebolt, J.S., Leopold, W.R. Cancer Chemother. Pharmacol. (1986) [Pubmed]
  5. CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Fukuda, M., Asano, S., Nakamura, T., Adachi, M., Yoshida, M., Yanagida, M., Nishida, E. Nature (1997) [Pubmed]
  6. Architecture of CRM1/Exportin1 suggests how cooperativity is achieved during formation of a nuclear export complex. Petosa, C., Schoehn, G., Askjaer, P., Bauer, U., Moulin, M., Steuerwald, U., Soler-López, M., Baudin, F., Mattaj, I.W., Müller, C.W. Mol. Cell (2004) [Pubmed]
  7. Temporal and spatial control of nucleophosmin by the Ran-Crm1 complex in centrosome duplication. Wang, W., Budhu, A., Forgues, M., Wang, X.W. Nat. Cell Biol. (2005) [Pubmed]
  8. Regulation of Stat3 nuclear export. Bhattacharya, S., Schindler, C. J. Clin. Invest. (2003) [Pubmed]
  9. Nuclear export of cyclin B1 and its possible role in the DNA damage-induced G2 checkpoint. Toyoshima, F., Moriguchi, T., Wada, A., Fukuda, M., Nishida, E. EMBO J. (1998) [Pubmed]
  10. Nuclear retention of IkappaBalpha protects it from signal-induced degradation and inhibits nuclear factor kappaB transcriptional activation. Rodriguez, M.S., Thompson, J., Hay, R.T., Dargemont, C. J. Biol. Chem. (1999) [Pubmed]
  11. Stat5B shuttles between cytoplasm and nucleus in a cytokine-dependent and -independent manner. Zeng, R., Aoki, Y., Yoshida, M., Arai, K., Watanabe, S. J. Immunol. (2002) [Pubmed]
  12. Nuclear export of the oncoprotein v-ErbA is mediated by acquisition of a viral nuclear export sequence. DeLong, L.J., Bonamy, G.M., Fink, E.N., Allison, L.A. J. Biol. Chem. (2004) [Pubmed]
  13. Nuclear export is required for degradation of endogenous p53 by MDM2 and human papillomavirus E6. Freedman, D.A., Levine, A.J. Mol. Cell. Biol. (1998) [Pubmed]
  14. The cytoplasmic shuttling and subsequent degradation of p27Kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex. Tomoda, K., Kubota, Y., Arata, Y., Mori, S., Maeda, M., Tanaka, T., Yoshida, M., Yoneda-Kato, N., Kato, J.Y. J. Biol. Chem. (2002) [Pubmed]
  15. Control of the nuclear-cytoplasmic partitioning of annexin II by a nuclear export signal and by p11 binding. Eberhard, D.A., Karns, L.R., VandenBerg, S.R., Creutz, C.E. J. Cell. Sci. (2001) [Pubmed]
  16. Nuclear export of influenza virus ribonucleoproteins: identification of an export intermediate at the nuclear periphery. Ma, K., Roy, A.M., Whittaker, G.R. Virology (2001) [Pubmed]
  17. The specificity of the CRM1-Rev nuclear export signal interaction is mediated by RanGTP. Askjaer, P., Jensen, T.H., Nilsson, J., Englmeier, L., Kjems, J. J. Biol. Chem. (1998) [Pubmed]
  18. Regulation of subcellular localization of the aryl hydrocarbon receptor (AhR). Richter, C.A., Tillitt, D.E., Hannink, M. Arch. Biochem. Biophys. (2001) [Pubmed]
  19. Abl interactor 1 (Abi-1) wave-binding and SNARE domains regulate its nucleocytoplasmic shuttling, lamellipodium localization, and wave-1 levels. Echarri, A., Lai, M.J., Robinson, M.R., Pendergast, A.M. Mol. Cell. Biol. (2004) [Pubmed]
  20. Role of the tetradecapeptide repeat domain of human histone deacetylase 6 in cytoplasmic retention. Bertos, N.R., Gilquin, B., Chan, G.K., Yen, T.J., Khochbin, S., Yang, X.J. J. Biol. Chem. (2004) [Pubmed]
  21. Biogenesis and nuclear export of ribosomal subunits in higher eukaryotes depend on the CRM1 export pathway. Thomas, F., Kutay, U. J. Cell. Sci. (2003) [Pubmed]
  22. Insights into a CRM1-mediated RNA-nuclear export pathway in Trypanosoma cruzi. Cuevas, I.C., Frasch, A.C., D'Orso, I. Mol. Biochem. Parasitol. (2005) [Pubmed]
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