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Gene Review

XPO1  -  exportin 1

Homo sapiens

Synonyms: CRM1, Chromosome region maintenance 1 protein homolog, Exp1, Exportin-1, emb, ...
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Disease relevance of XPO1


Psychiatry related information on XPO1


High impact information on XPO1

  • We show that DDX3 is a nucleo-cytoplasmic shuttling protein, which binds CRM1 and localizes to nuclear membrane pores [7].
  • In vivo, PHAX is required for U snRNA export but not for CRM1-mediated export in general [8].
  • Conversely, leptomycin B, a cytotoxin that is shown to bind to CRM1 protein, specifically inhibits the nuclear export of Rev and U snRNAs [9].
  • 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 [9].
  • CRM1 is distantly related to receptors that mediate nuclear protein import and was previously shown to interact with the nuclear pore complex [9].

Chemical compound and disease context of XPO1


Biological context of XPO1


Anatomical context of XPO1

  • Our results are consistent with the hypothesis that the Ran-Crm1 complex may promote a local enrichment of NPM on centrosomes, thereby preventing centrosome reduplication [18].
  • We recently developed an assay in which nuclear export of the shuttling transcription factor NFAT (nuclear factor of activated T cells) can be reconstituted in permeabilized cells with the GTPase Ran and the nuclear export receptor CRM1 [19].
  • A role for RanBP1 in the release of CRM1 from the nuclear pore complex in a terminal step of nuclear export [19].
  • In CAN-/- mouse embryos lacking CAN, hCRM1 remained in the nuclear envelope, suggesting that this protein can also bind to other repeat-containing nucleoporins [13].
  • After preincubation of permeabilized cells with a Ran mutant that cannot hydrolyze GTP (RanQ69L), cytosol supports NFAT export, but CRM1 and Ran alone do not [19].

Associations of XPO1 with chemical compounds


Physical interactions of XPO1


Enzymatic interactions of XPO1

  • Results indicate that STAT1 can be dephosphorylated in the nucleus and actively exported by the chromosome region maintenance 1 (CRM1) export receptor [25].

Regulatory relationships of XPO1

  • These observations demonstrate that INI1 has a masked NES that mediates regulated hCRM1/exportin1-dependent nuclear export and we propose that mutations that cause deregulated nuclear export of the protein could lead to tumorigenesis [28].
  • RanBP3 stimulates export by enhancing the affinity of Crm1 for Ran.GTP and cargo [21].
  • NXF3-dependent RNA export is therefore blocked by Crm1-specific inhibitors that do not affect TAP function [29].
  • Thus, NXT1 regulates the Crm1-dependent export pathway through its direct interaction with Ran-GTP [30].
  • We have identified the mechanism of XAP-2-induced cytoplasmic localization of the receptor and studied the potential cross-talk between CRM-1 and XAP-2 [31].

Other interactions of XPO1

  • RanBP1 as well as Ran-binding domains of the cytoplasmic nucleoporin RanBP2 promote the release of CRM1 from the NPC [19].
  • Full-length INI1 specifically associated with hCRM1/exportin1 in vivo and in vitro [28].
  • Under the same conditions, the steady-state subcellular localization of other nuclear or cytoplasmic proteins and CRM1-mediated protein export are not detectably affected, indicating that the release of NXF1 into the cytoplasm and the inhibition of mRNA export are not due to a general defect in NPC function [32].
  • RanBP3 could also promote binding of Crm1 to RCC1 in the presence of Ran [21].
  • The RanQ69L preincubation leads to accumulation of CRM1 at the cytoplasmic periphery of the nuclear pore complex (NPC) in association with the p62 complex and Can/Nup214 [19].

Analytical, diagnostic and therapeutic context of XPO1


  1. Nucleoporins nup98 and nup214 participate in nuclear export of human immunodeficiency virus type 1 Rev. Zolotukhin, A.S., Felber, B.K. J. Virol. (1999) [Pubmed]
  2. Association with the cellular export receptor CRM 1 mediates function and intracellular localization of Epstein-Barr virus SM protein, a regulator of gene expression. Boyle, S.M., Ruvolo, V., Gupta, A.K., Swaminathan, S. J. Virol. (1999) [Pubmed]
  3. Involvement of Crm1 in hepatitis B virus X protein-induced aberrant centriole replication and abnormal mitotic spindles. Forgues, M., Difilippantonio, M.J., Linke, S.P., Ried, T., Nagashima, K., Feden, J., Valerie, K., Fukasawa, K., Wang, X.W. Mol. Cell. Biol. (2003) [Pubmed]
  4. 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]
  5. Central infusions of the recombinant human prolactin receptor antagonist, S179D-PRL, delay the onset of maternal behavior in steroid-primed, nulliparous female rats. Bridges, R., Rigero, B., Byrnes, E., Yang, L., Walker, A. Endocrinology (2001) [Pubmed]
  6. Tiagabine reduces ethanol reward in C57BL/6 mice under acute and chronic administration regimens. Nguyen, S.A., Deleon, C.P., Malcolm, R.J., Middaugh, L.D. Synapse (2005) [Pubmed]
  7. Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function. Yedavalli, V.S., Neuveut, C., Chi, Y.H., Kleiman, L., Jeang, K.T. Cell (2004) [Pubmed]
  8. PHAX, a mediator of U snRNA nuclear export whose activity is regulated by phosphorylation. Ohno, M., Segref, A., Bachi, A., Wilm, M., Mattaj, I.W. Cell (2000) [Pubmed]
  9. CRM1 is an export receptor for leucine-rich nuclear export signals. Fornerod, M., Ohno, M., Yoshida, M., Mattaj, I.W. Cell (1997) [Pubmed]
  10. 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]
  11. A methionine-rich domain mediates CRM1-dependent nuclear export activity of Borna disease virus phosphoprotein. Yanai, H., Kobayashi, T., Hayashi, Y., Watanabe, Y., Ohtaki, N., Zhang, G., de la Torre, J.C., Ikuta, K., Tomonaga, K. J. Virol. (2006) [Pubmed]
  12. Sequence of Crm1/exportin 1 mutant alleles reveals critical sites associated with multidrug resistance. Carobbio, S., Realini, C., Norbury, C.J., Toda, T., Cavalli, F., Spataro, V. Curr. Genet. (2001) [Pubmed]
  13. The human homologue of yeast CRM1 is in a dynamic subcomplex with CAN/Nup214 and a novel nuclear pore component Nup88. Fornerod, M., van Deursen, J., van Baal, S., Reynolds, A., Davis, D., Murti, K.G., Fransen, J., Grosveld, G. EMBO J. (1997) [Pubmed]
  14. Nuclear export of ERK3 by a CRM1-dependent mechanism regulates its inhibitory action on cell cycle progression. Julien, C., Coulombe, P., Meloche, S. J. Biol. Chem. (2003) [Pubmed]
  15. The zinc finger cluster domain of RanBP2 is a specific docking site for the nuclear export factor, exportin-1. Singh, B.B., Patel, H.H., Roepman, R., Schick, D., Ferreira, P.A. J. Biol. Chem. (1999) [Pubmed]
  16. Nup358/RanBP2 attaches to the nuclear pore complex via association with Nup88 and Nup214/CAN and plays a supporting role in CRM1-mediated nuclear protein export. Bernad, R., van der Velde, H., Fornerod, M., Pickersgill, H. Mol. Cell. Biol. (2004) [Pubmed]
  17. Overexpression of the nucleoporin CAN/NUP214 induces growth arrest, nucleocytoplasmic transport defects, and apoptosis. Boer, J., Bonten-Surtel, J., Grosveld, G. Mol. Cell. Biol. (1998) [Pubmed]
  18. 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]
  19. A role for RanBP1 in the release of CRM1 from the nuclear pore complex in a terminal step of nuclear export. Kehlenbach, R.H., Dickmanns, A., Kehlenbach, A., Guan, T., Gerace, L. J. Cell Biol. (1999) [Pubmed]
  20. 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]
  21. Ran-binding protein 3 links Crm1 to the Ran guanine nucleotide exchange factor. Nemergut, M.E., Lindsay, M.E., Brownawell, A.M., Macara, I.G. J. Biol. Chem. (2002) [Pubmed]
  22. 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]
  23. PHAX and CRM1 are required sequentially to transport U3 snoRNA to nucleoli. Boulon, S., Verheggen, C., Jady, B.E., Girard, C., Pescia, C., Paul, C., Ospina, J.K., Kiss, T., Matera, A.G., Bordonné, R., Bertrand, E. Mol. Cell (2004) [Pubmed]
  24. NXT1 is necessary for the terminal step of Crm1-mediated nuclear export. Black, B.E., Holaska, J.M., Lévesque, L., Ossareh-Nazari, B., Gwizdek, C., Dargemont, C., Paschal, B.M. J. Cell Biol. (2001) [Pubmed]
  25. Nuclear export signal located within theDNA-binding domain of the STAT1transcription factor. McBride, K.M., McDonald, C., Reich, N.C. EMBO J. (2000) [Pubmed]
  26. Separate nuclear import pathways converge on the nucleoporin Nup153 and can be dissected with dominant-negative inhibitors. Shah, S., Forbes, D.J. Curr. Biol. (1998) [Pubmed]
  27. An ancient family of human endogenous retroviruses encodes a functional homolog of the HIV-1 Rev protein. Yang, J., Bogerd, H.P., Peng, S., Wiegand, H., Truant, R., Cullen, B.R. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  28. A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export: implications for tumorigenesis. Craig, E., Zhang, Z.K., Davies, K.P., Kalpana, G.V. EMBO J. (2002) [Pubmed]
  29. Two closely related human nuclear export factors utilize entirely distinct export pathways. Yang, J., Bogerd, H.P., Wang, P.J., Page, D.C., Cullen, B.R. Mol. Cell (2001) [Pubmed]
  30. Identification of an NTF2-related factor that binds Ran-GTP and regulates nuclear protein export. Black, B.E., Lévesque, L., Holaska, J.M., Wood, T.C., Paschal, B.M. Mol. Cell. Biol. (1999) [Pubmed]
  31. Two parallel pathways mediate cytoplasmic localization of the dioxin (aryl hydrocarbon) receptor. Berg, P., Pongratz, I. J. Biol. Chem. (2002) [Pubmed]
  32. RanBP2/Nup358 provides a major binding site for NXF1-p15 dimers at the nuclear pore complex and functions in nuclear mRNA export. Forler, D., Rabut, G., Ciccarelli, F.D., Herold, A., Köcher, T., Niggeweg, R., Bork, P., Ellenberg, J., Izaurralde, E. Mol. Cell. Biol. (2004) [Pubmed]
  33. Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export. Ishida, N., Hara, T., Kamura, T., Yoshida, M., Nakayama, K., Nakayama, K.I. J. Biol. Chem. (2002) [Pubmed]
  34. 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]
  35. Molecular cloning and cell cycle-dependent expression of mammalian CRM1, a protein involved in nuclear export of proteins. Kudo, N., Khochbin, S., Nishi, K., Kitano, K., Yanagida, M., Yoshida, M., Horinouchi, S. J. Biol. Chem. (1997) [Pubmed]
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