XPO1

XPO1 (CRM1) originally was identified in the fission yeast Schizosaccharomyces pombe in a genetic screen, and investigators determined that it was involved in control of the chromosome structure.{{Cite journal|last1=Adachi|first1=Y.|last2=Yanagida|first2=M.|date=1989-04-01|title=Higher order chromosome structure is affected by cold-sensitive mutations in a Schizosaccharomyces pombe gene crm1+ which encodes a 115-kD protein preferentially localized in the nucleus and its periphery.|journal=Journal of Cell Biology|language=en|volume=108|issue=4|pages=1195–1207| pmc=2115495|doi=10.1083/jcb.108.4.1195|pmid=2647765 |issn=0021-9525|doi-access=free}} It was later shown to be the nuclear transport receptor for cargos with leucine-rich nuclear export signals (NES).{{Cite journal|last1=Fornerod|first1=M.|last2=Ohno|first2=M.|last3=Yoshida|first3=M.|last4=Mattaj|first4=I. W.|date=1997-09-19|title=CRM1 is an export receptor for leucine-rich nuclear export signals|journal=Cell|volume=90|issue=6|pages=1051–1060|doi=10.1016/s0092-8674(00)80371-2|issn=0092-8674|pmid=9323133|doi-access=free}}{{Cite journal|last1=Fukuda|first1=M.|last2=Asano|first2=S.|last3=Nakamura|first3=T.|last4=Adachi|first4=M.|last5=Yoshida|first5=M.|last6=Yanagida|first6=M.|last7=Nishida|first7=E.|date=1997-11-20|title=CRM1 is responsible for intracellular transport mediated by the nuclear export signal|url=https://pubmed.ncbi.nlm.nih.gov/9384386|journal=Nature|volume=390|issue=6657|pages=308–311|doi=10.1038/36894|issn=0028-0836|pmid=9384386|bibcode=1997Natur.390..308F |s2cid=4420607 }}{{Cite journal|last1=Stade|first1=K.|last2=Ford|first2=C. S.|last3=Guthrie|first3=C.|last4=Weis|first4=K.|date=1997-09-19|title=Exportin 1 (Crm1p) is an essential nuclear export factor|journal=Cell|volume=90|issue=6|pages=1041–1050|doi=10.1016/s0092-8674(00)80370-0|issn=0092-8674|pmid=9323132|doi-access=free}}{{Cite journal|last1=Ossareh-Nazari|first1=B.|last2=Bachelerie|first2=F.|last3=Dargemont|first3=C.|date=1997-10-03|title=Evidence for a role of CRM1 in signal-mediated nuclear protein export|url=https://pubmed.ncbi.nlm.nih.gov/9311922|journal=Science|volume=278|issue=5335|pages=141–144|doi=10.1126/science.278.5335.141|issn=0036-8075|pmid=9311922}} The structural details of the interaction of XPO1 with its cargos were revealed two decades after the gene was identified.{{Cite journal|last1=Monecke|first1=Thomas|last2=Güttler|first2=Thomas|last3=Neumann|first3=Piotr|last4=Dickmanns|first4=Achim|last5=Görlich|first5=Dirk|last6=Ficner|first6=Ralf|date=2009-05-22|title=Crystal structure of the nuclear export receptor CRM1 in complex with Snurportin1 and RanGTP|journal=Science|volume=324|issue=5930|pages=1087–1091|doi=10.1126/science.1173388|issn=1095-9203|pmid=19389996|bibcode=2009Sci...324.1087M |s2cid=21116091 |doi-access=free}}{{Cite journal|last1=Dong|first1=Xiuhua|last2=Biswas|first2=Anindita|last3=Süel|first3=Katherine E.|last4=Jackson|first4=Laurie K.|last5=Martinez|first5=Rita|last6=Gu|first6=Hongmei|last7=Chook|first7=Yuh Min|date=2009-04-30|title=Structural basis for leucine-rich nuclear export signal recognition by CRM1|journal=Nature|volume=458|issue=7242|pages=1136–1141|doi=10.1038/nature07975|issn=1476-4687|pmc=3437623|pmid=19339969|bibcode=2009Natur.458.1136D }}{{Cite journal|last1=Dong|first1=Xiuhua|last2=Biswas|first2=Anindita|last3=Chook|first3=Yuh Min|date=May 2009|title=Structural basis for assembly and disassembly of the CRM1 nuclear export complex|journal=Nature Structural & Molecular Biology|volume=16|issue=5|pages=558–560|doi=10.1038/nsmb.1586|issn=1545-9985|pmc=3437629|pmid=19339972}}{{Cite journal|last1=Güttler|first1=Thomas|last2=Madl|first2=Tobias|last3=Neumann|first3=Piotr|last4=Deichsel|first4=Danilo|last5=Corsini|first5=Lorenzo|last6=Monecke|first6=Thomas|last7=Ficner|first7=Ralf|last8=Sattler|first8=Michael|last9=Görlich|first9=Dirk|date=November 2010|title=NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1|url=https://pubmed.ncbi.nlm.nih.gov/20972448|journal=Nature Structural & Molecular Biology|volume=17|issue=11|pages=1367–1376|doi=10.1038/nsmb.1931|issn=1545-9985|pmid=20972448|hdl=11858/00-001M-0000-0012-D4DB-B|s2cid=21593381 |hdl-access=free}}

XPO1 mediates NES-dependent protein transport. It exports several hundreds of different proteins from the nucleus.{{Cite journal|last1=Thakar|first1=Ketan|last2=Karaca|first2=Samir|last3=Port|first3=Sarah A.|last4=Urlaub|first4=Henning|last5=Kehlenbach|first5=Ralph H.|date=March 2013|title=Identification of CRM1-dependent Nuclear Export Cargos Using Quantitative Mass Spectrometry|journal=Molecular & Cellular Proteomics |volume=12|issue=3|pages=664–678|doi=10.1074/mcp.M112.024877|issn=1535-9484|pmc=3591659|pmid=23242554 |doi-access=free }}{{Cite journal|last1=Kırlı|first1=Koray|last2=Karaca|first2=Samir|last3=Dehne|first3=Heinz Jürgen|last4=Samwer|first4=Matthias|last5=Pan|first5=Kuan Ting|last6=Lenz|first6=Christof|last7=Urlaub|first7=Henning|last8=Görlich|first8=Dirk|date=2015-12-17|title=A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning|journal=eLife|volume=4|doi=10.7554/eLife.11466|issn=2050-084X|pmc=4764573|pmid=26673895 |doi-access=free }} XPO1 is involved in the nuclear export of ribosomal subunits.{{Cite journal|last1=Moy|first1=T. I.|last2=Silver|first2=P. A.|date=1999-08-15|title=Nuclear export of the small ribosomal subunit requires the ran-GTPase cycle and certain nucleoporins|journal=Genes & Development|volume=13|issue=16|pages=2118–2133|doi=10.1101/gad.13.16.2118|issn=0890-9369|pmc=316945|pmid=10465789}}{{Cite journal|last1=Ho|first1=J. H.|last2=Kallstrom|first2=G.|last3=Johnson|first3=A. W.|date=2000-11-27|title=Nmd3p is a Crm1p-dependent adapter protein for nuclear export of the large ribosomal subunit|journal=The Journal of Cell Biology|volume=151|issue=5|pages=1057–1066|doi=10.1083/jcb.151.5.1057|issn=0021-9525|pmc=2174350|pmid=11086007}}{{Cite journal|last1=Zemp|first1=Ivo|last2=Wild|first2=Thomas|last3=O'Donohue|first3=Marie-Françoise|last4=Wandrey|first4=Franziska|last5=Widmann|first5=Barbara|last6=Gleizes|first6=Pierre-Emmanuel|last7=Kutay|first7=Ulrike|date=2009-06-29|title=Distinct cytoplasmic maturation steps of 40S ribosomal subunit precursors require hRio2|journal=The Journal of Cell Biology|volume=185|issue=7|pages=1167–1180|doi=10.1083/jcb.200904048|issn=1540-8140|pmc=2712965|pmid=19564402}} XPO1 plays a role in export of various RNAs including U snRNAs, rRNAs (as a part of ribosomal subunits), and some mRNAs.{{Cite journal|last=Cullen|first=B. R.|date=June 2000|title=Nuclear RNA export pathways|journal=Molecular and Cellular Biology|volume=20|issue=12|pages=4181–4187|doi=10.1128/mcb.20.12.4181-4187.2000|issn=0270-7306|pmc=85787|pmid=10825183}}{{Cite journal|last1=Köhler|first1=Alwin|last2=Hurt|first2=Ed|date=October 2007|title=Exporting RNA from the nucleus to the cytoplasm|url=https://www.nature.com/articles/nrm2255|journal=Nature Reviews Molecular Cell Biology|language=en|volume=8|issue=10|pages=761–773|doi=10.1038/nrm2255|pmid=17786152 |s2cid=10836137 |issn=1471-0080|url-access=subscription}}{{Cite journal|date=2016-05-22|title=Nucleocytoplasmic Transport of RNAs and RNA–Protein Complexes|journal=Journal of Molecular Biology|language=en|volume=428|issue=10|pages=2040–2059|doi=10.1016/j.jmb.2015.09.023|issn=0022-2836|doi-access=free|last1=Sloan |first1=Katherine E. |last2=Gleizes |first2=Pierre-Emmanuel |last3=Bohnsack |first3=Markus T. |pmid=26434509 }}

XPO1 is involved in various viral infections. For example, it is required for the nuclear export of HIV-1 RNA in complex with the viral protein Rev, an event that is a crucial part of the infection cycle.{{Cite journal|last1=Booth|first1=David S|last2=Cheng|first2=Yifan|last3=Frankel|first3=Alan D|date=2014-12-08|editor-last=Sundquist|editor-first=Wesley I|title=The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA|journal=eLife|volume=3|pages=e04121|pmid=25486595 |doi=10.7554/eLife.04121|pmc=4360530 |issn=2050-084X|doi-access=free}} XPO1 is affected in some cancer types {{Cite journal|last1=Taylor|first1=Justin|last2=Sendino|first2=Maria|last3=Gorelick|first3=Alexander N.|last4=Pastore|first4=Alessandro|last5=Chang|first5=Matthew T.|last6=Penson|first6=Alexander V.|last7=Gavrila|first7=Elena I.|last8=Stewart|first8=Connor|last9=Melnik|first9=Ella M.|last10=Herrejon Chavez|first10=Florisela|last11=Bitner|first11=Lillian|date=October 2019|title=Altered Nuclear Export Signal Recognition as a Driver of Oncogenesis|journal=Cancer Discovery|volume=9|issue=10|pages=1452–1467|doi=10.1158/2159-8290.CD-19-0298|issn=2159-8290|pmc=6774834|pmid=31285298}} and is therefore viewed as a target for development of anti-cancer drugs.{{Cite journal|last1=Fung|first1=Ho Yee Joyce|last2=Chook|first2=Yuh Min|date=August 2014|title=Atomic basis of CRM1-cargo recognition, release and inhibition|journal=Seminars in Cancer Biology|volume=27|pages=52–61|doi=10.1016/j.semcancer.2014.03.002|issn=1096-3650|pmc=4108548|pmid=24631835}} Selinexor, a drug specifically targeting XPO1, was approved by the FDA for treatment of multiple myeloma.{{Cite journal|last=Research|first=Center for Drug Evaluation and|date=2019-12-20|title=FDA grants accelerated approval to selinexor for multiple myeloma|url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-selinexor-multiple-myeloma|archive-url=https://web.archive.org/web/20190928072302/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-selinexor-multiple-myeloma|url-status=dead|archive-date=September 28, 2019|journal=FDA|language=en}}

XPO1 has been shown to interact with:

{{div col|colwidth=20em}}

• APC,
• CDKN1B,{{cite journal | vauthors = Ishida N, Hara T, Kamura T, Yoshida M, Nakayama K, Nakayama KI | title = Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export | journal = J. Biol. Chem. | volume = 277 | issue = 17 | pages = 14355–8 | date = April 2002 | pmid = 11889117 | doi = 10.1074/jbc.C100762200 | doi-access = free }}{{cite journal | vauthors = Connor MK, Kotchetkov R, Cariou S, Resch A, Lupetti R, Beniston RG, Melchior F, Hengst L, Slingerland JM | title = CRM1/Ran-mediated nuclear export of p27(Kip1) involves a nuclear export signal and links p27 export and proteolysis | journal = Mol. Biol. Cell | volume = 14 | issue = 1 | pages = 201–13 | date = January 2003 | pmid = 12529437 | pmc = 140238 | doi = 10.1091/mbc.E02-06-0319 }}
• CIITA,{{cite journal | vauthors = Raval A, Weissman JD, Howcroft TK, Singer DS | title = The GTP-binding domain of class II transactivator regulates its nuclear export | journal = J. Immunol. | volume = 170 | issue = 2 | pages = 922–30 | date = January 2003 | pmid = 12517958 | doi = 10.4049/jimmunol.170.2.922| doi-access = free }}{{cite journal | vauthors = Voong LN, Slater AR, Kratovac S, Cressman DE | title = Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator | journal = J. Biol. Chem. | volume = 283 | issue = 14 | pages = 9031–9 | date = April 2008 | pmid = 18245089 | pmc = 2431044 | doi = 10.1074/jbc.M706487200 | doi-access = free }}
• NMD3,{{cite journal | vauthors = Thomas F, Kutay U | title = Biogenesis and nuclear export of ribosomal subunits in higher eukaryotes depend on the CRM1 export pathway | journal = J. Cell Sci. | volume = 116 | issue = Pt 12 | pages = 2409–19 | date = June 2003 | pmid = 12724356 | doi = 10.1242/jcs.00464 | doi-access = free }}
• Nucleoporin 62,{{cite journal | vauthors = Kehlenbach RH, Dickmanns A, Kehlenbach A, Guan T, Gerace L | title = A role for RanBP1 in the release of CRM1 from the nuclear pore complex in a terminal step of nuclear export | journal = J. Cell Biol. | volume = 145 | issue = 4 | pages = 645–57 | date = May 1999 | pmid = 10330396 | pmc = 2133185 | doi = 10.1083/jcb.145.4.645}}
• RANBP1,{{cite journal | vauthors = Singh BB, Patel HH, Roepman R, Schick D, Ferreira PA | title = The zinc finger cluster domain of RanBP2 is a specific docking site for the nuclear export factor, exportin-1 | journal = J. Biol. Chem. | volume = 274 | issue = 52 | pages = 37370–8 | date = Dec 1999 | pmid = 10601307 | doi = 10.1074/jbc.274.52.37370| doi-access = free | hdl = 2066/120791 | hdl-access = free }}
• RANBP3,{{cite journal | vauthors = Lindsay ME, Holaska JM, Welch K, Paschal BM, Macara IG | title = Ran-binding protein 3 is a cofactor for Crm1-mediated nuclear protein export | journal = J. Cell Biol. | volume = 153 | issue = 7 | pages = 1391–402 | date = June 2001 | pmid = 11425870 | pmc = 2150735 | doi = 10.1083/jcb.153.7.1391}}{{cite journal | vauthors = Lindsay ME, Plafker K, Smith AE, Clurman BE, Macara IG | title = Npap60/Nup50 is a tri-stable switch that stimulates importin-alpha:beta-mediated nuclear protein import | journal = Cell | volume = 110 | issue = 3 | pages = 349–60 | date = August 2002 | pmid = 12176322 | doi = 10.1016/s0092-8674(02)00836-x| s2cid = 15515037 | doi-access = free }}
• Ran,{{cite journal | vauthors = Tickenbrock L, Cramer J, Vetter IR, Muller O | title = The coiled coil region (amino acids 129-250) of the tumor suppressor protein adenomatous polyposis coli (APC). Its structure and its interaction with chromosome maintenance region 1 (Crm-1) | journal = J. Biol. Chem. | volume = 277 | issue = 35 | pages = 32332–8 | date = August 2002 | pmid = 12070164 | doi = 10.1074/jbc.M203990200 | doi-access = free }}{{cite journal | vauthors = Plafker K, Macara IG | title = Facilitated nucleocytoplasmic shuttling of the Ran binding protein RanBP1 | journal = Mol. Cell. Biol. | volume = 20 | issue = 10 | pages = 3510–21 | date = May 2000 | pmid = 10779340 | pmc = 85643 | doi = 10.1128/mcb.20.10.3510-3521.2000}}{{cite journal | vauthors = Fornerod M, Ohno M, Yoshida M, Mattaj IW | title = CRM1 is an export receptor for leucine-rich nuclear export signals | journal = Cell | volume = 90 | issue = 6 | pages = 1051–60 | date = September 1997 | pmid = 9323133 | doi = 10.1016/s0092-8674(00)80371-2| s2cid = 15119502 | doi-access = free }}
• SMARCB1,{{cite journal | vauthors = Craig E, Zhang ZK, Davies KP, Kalpana GV | title = A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export: implications for tumorigenesis | journal = EMBO J. | volume = 21 | issue = 1–2 | pages = 31–42 | date = January 2002 | pmid = 11782423 | pmc = 125819 | doi = 10.1093/emboj/21.1.31 }} and
• p53.{{cite journal | vauthors = Kanai M, Hanashiro K, Kim SH, Hanai S, Boulares AH, Miwa M, Fukasawa K | title = Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation | journal = Nat. Cell Biol. | volume = 9 | issue = 10 | pages = 1175–83 | date = September 2007 | pmid = 17891139 | doi = 10.1038/ncb1638 | s2cid = 13433567 }}{{cite journal | vauthors = Shao C, Lu C, Chen L, Koty PP, Cobos E, Gao W | title = p53-Dependent anticancer effects of leptomycin B on lung adenocarcinoma | journal = Cancer Chemother. Pharmacol. | volume = 67 | issue = 6 | pages = 1369–80 | date = August 2010 | pmid = 20803015 | doi = 10.1007/s00280-010-1434-6 | s2cid = 27127578 }}

{{Div col end}}

• Karyopherin
• Importin
• Nuclear transport
• Nuclear export signal

{{Reflist|2}}

{{Refbegin | 2}}

• {{cite journal | vauthors = Görlich D, Kutay U | title = Transport between the cell nucleus and the cytoplasm. | journal = Annu. Rev. Cell Dev. Biol. | volume = 15 | issue = 1 | pages = 607–60 | year = 1999 | pmid = 10611974 | doi = 10.1146/annurev.cellbio.15.1.607 }}
• {{cite journal | vauthors = Budhu AS, Wang XW | title = Loading and unloading: orchestrating centrosome duplication and spindle assembly by Ran/Crm1. | journal = Cell Cycle | volume = 4 | issue = 11 | pages = 1510–4 | year = 2007 | pmid = 16294017 | pmc = 1402358 | doi = 10.4161/cc.4.11.2187 }}
• {{cite journal | vauthors = Li L, Li HS, Pauza CD, Bukrinsky M, Zhao RY | title = Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions. | journal = Cell Res. | volume = 15 | issue = 11–12 | pages = 923–34 | year = 2006 | pmid = 16354571 | doi = 10.1038/sj.cr.7290370 | doi-access = free }}
• {{cite journal | vauthors = Stauber RH, Mann W, Knauer SK | title = Nuclear and cytoplasmic survivin: molecular mechanism, prognostic, and therapeutic potential. | journal = Cancer Res. | volume = 67 | issue = 13 | pages = 5999–6002 | year = 2007 | pmid = 17616652 | doi = 10.1158/0008-5472.CAN-07-0494 | doi-access = free }}
• {{cite journal | vauthors = Mathew C, Ghildyal R | title = CRM1 inhibitors for antiviral therapy. | journal = Frontiers in Microbiology | volume = 8 | pages = 1171 | year = 2017 | pmid = 28702009 | pmc = 5487384 | doi = 10.3389/fmicb.2017.01171 | doi-access = free }}

{{Refend}}

• [http://www.pdbe.org/emsearch/crm1 3D electron microscopy structures of CRM1 from the EM Data Bank(EMDB)]

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{{Gene-2-stub}}

Category:Long stubs with short prose