From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
Exportin 1 (XPO1 ), also known as chromosomal region maintenance 1 (CRM1 ), is a eukaryotic protein that mediates the nuclear export of various proteins and RNAs.
History
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.
[5] It was later shown to be the
nuclear transport receptor for cargos with leucine-rich nuclear export signals (
NES ).
[6]
[7]
[8]
[9] The structural details of the interaction of XPO1 with its cargos were revealed two decades after the gene was identified.
[10]
[11]
[12]
[13]
Function
XPO1 mediates NES-dependent protein transport. It exports several hundreds of different proteins from the nucleus.
[14]
[15] XPO1 is involved in the nuclear export of ribosomal subunits.
[16]
[17]
[18] XPO1 plays a role in export of various RNAs including U snRNAs, rRNAs (as a part of ribosomal subunits), and some mRNAs.
[19]
[20]
[21]
Medical relevance
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.
[22] XPO1 is affected in some
cancer types
[23] and is therefore viewed as a target for development of anti-cancer drugs.
[24]
Selinexor , a drug specifically targeting XPO1, was approved by the
FDA for treatment of multiple myeloma.
[25]
Interactions
XPO1 has been shown to
interact with:
See also
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000082898 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000020290 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Adachi Y, Yanagida M (1989-04-01).
"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 of Cell Biology . 108 (4): 1195–1207.
doi :
10.1083/jcb.108.4.1195 .
ISSN
0021-9525 .
PMC
2115495 .
PMID
2647765 .
^ Fornerod M, Ohno M, Yoshida M, Mattaj IW (1997-09-19).
"CRM1 is an export receptor for leucine-rich nuclear export signals" . Cell . 90 (6): 1051–1060.
doi :
10.1016/s0092-8674(00)80371-2 .
ISSN
0092-8674 .
PMID
9323133 .
^ Fukuda M, Asano S, Nakamura T, Adachi M, Yoshida M, Yanagida M, Nishida E (1997-11-20).
"CRM1 is responsible for intracellular transport mediated by the nuclear export signal" . Nature . 390 (6657): 308–311.
Bibcode :
1997Natur.390..308F .
doi :
10.1038/36894 .
ISSN
0028-0836 .
PMID
9384386 .
S2CID
4420607 .
^ Stade K, Ford CS, Guthrie C, Weis K (1997-09-19).
"Exportin 1 (Crm1p) is an essential nuclear export factor" . Cell . 90 (6): 1041–1050.
doi :
10.1016/s0092-8674(00)80370-0 .
ISSN
0092-8674 .
PMID
9323132 .
^ Ossareh-Nazari B, Bachelerie F, Dargemont C (1997-10-03).
"Evidence for a role of CRM1 in signal-mediated nuclear protein export" . Science . 278 (5335): 141–144.
doi :
10.1126/science.278.5335.141 .
ISSN
0036-8075 .
PMID
9311922 .
^ Monecke T, Güttler T, Neumann P, Dickmanns A, Görlich D, Ficner R (2009-05-22).
"Crystal structure of the nuclear export receptor CRM1 in complex with Snurportin1 and RanGTP" . Science . 324 (5930): 1087–1091.
Bibcode :
2009Sci...324.1087M .
doi :
10.1126/science.1173388 .
ISSN
1095-9203 .
PMID
19389996 .
S2CID
21116091 .
^ Dong X, Biswas A, Süel KE, Jackson LK, Martinez R, Gu H, Chook YM (2009-04-30).
"Structural basis for leucine-rich nuclear export signal recognition by CRM1" . Nature . 458 (7242): 1136–1141.
Bibcode :
2009Natur.458.1136D .
doi :
10.1038/nature07975 .
ISSN
1476-4687 .
PMC
3437623 .
PMID
19339969 .
^ Dong X, Biswas A, Chook YM (May 2009).
"Structural basis for assembly and disassembly of the CRM1 nuclear export complex" . Nature Structural & Molecular Biology . 16 (5): 558–560.
doi :
10.1038/nsmb.1586 .
ISSN
1545-9985 .
PMC
3437629 .
PMID
19339972 .
^ Güttler T, Madl T, Neumann P, Deichsel D, Corsini L, Monecke T, Ficner R, Sattler M, Görlich D (November 2010).
"NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1" . Nature Structural & Molecular Biology . 17 (11): 1367–1376.
doi :
10.1038/nsmb.1931 .
hdl :
11858/00-001M-0000-0012-D4DB-B .
ISSN
1545-9985 .
PMID
20972448 .
S2CID
21593381 .
^ Thakar K, Karaca S, Port SA, Urlaub H, Kehlenbach RH (March 2013).
"Identification of CRM1-dependent Nuclear Export Cargos Using Quantitative Mass Spectrometry" . Molecular & Cellular Proteomics . 12 (3): 664–678.
doi :
10.1074/mcp.M112.024877 .
ISSN
1535-9484 .
PMC
3591659 .
PMID
23242554 .
^ Kırlı K, Karaca S, Dehne HJ, Samwer M, Pan KT, Lenz C, Urlaub H, Görlich D (2015-12-17).
"A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning" . eLife . 4 .
doi :
10.7554/eLife.11466 .
ISSN
2050-084X .
PMC
4764573 .
PMID
26673895 .
^ Moy TI, Silver PA (1999-08-15).
"Nuclear export of the small ribosomal subunit requires the ran-GTPase cycle and certain nucleoporins" . Genes & Development . 13 (16): 2118–2133.
doi :
10.1101/gad.13.16.2118 .
ISSN
0890-9369 .
PMC
316945 .
PMID
10465789 .
^ Ho JH, Kallstrom G, Johnson AW (2000-11-27).
"Nmd3p is a Crm1p-dependent adapter protein for nuclear export of the large ribosomal subunit" . The Journal of Cell Biology . 151 (5): 1057–1066.
doi :
10.1083/jcb.151.5.1057 .
ISSN
0021-9525 .
PMC
2174350 .
PMID
11086007 .
^ Zemp I, Wild T, O'Donohue MF, Wandrey F, Widmann B, Gleizes PE, Kutay U (2009-06-29).
"Distinct cytoplasmic maturation steps of 40S ribosomal subunit precursors require hRio2" . The Journal of Cell Biology . 185 (7): 1167–1180.
doi :
10.1083/jcb.200904048 .
ISSN
1540-8140 .
PMC
2712965 .
PMID
19564402 .
^ Cullen BR (June 2000).
"Nuclear RNA export pathways" . Molecular and Cellular Biology . 20 (12): 4181–4187.
doi :
10.1128/mcb.20.12.4181-4187.2000 .
ISSN
0270-7306 .
PMC
85787 .
PMID
10825183 .
^ Köhler A, Hurt E (October 2007).
"Exporting RNA from the nucleus to the cytoplasm" . Nature Reviews Molecular Cell Biology . 8 (10): 761–773.
doi :
10.1038/nrm2255 .
ISSN
1471-0080 .
PMID
17786152 .
S2CID
10836137 .
^ Sloan KE, Gleizes PE, Bohnsack MT (2016-05-22).
"Nucleocytoplasmic Transport of RNAs and RNA–Protein Complexes" . Journal of Molecular Biology . 428 (10): 2040–2059.
doi :
10.1016/j.jmb.2015.09.023 .
ISSN
0022-2836 .
PMID
26434509 .
^ Booth DS, Cheng Y, Frankel AD (2014-12-08). Sundquist WI (ed.).
"The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA" . eLife . 3 : e04121.
doi :
10.7554/eLife.04121 .
ISSN
2050-084X .
PMC
4360530 .
PMID
25486595 .
^ Taylor J, Sendino M, Gorelick AN, Pastore A, Chang MT, Penson AV, Gavrila EI, Stewart C, Melnik EM, Herrejon Chavez F, Bitner L (October 2019).
"Altered Nuclear Export Signal Recognition as a Driver of Oncogenesis" . Cancer Discovery . 9 (10): 1452–1467.
doi :
10.1158/2159-8290.CD-19-0298 .
ISSN
2159-8290 .
PMC
6774834 .
PMID
31285298 .
^ Fung HY, Chook YM (August 2014).
"Atomic basis of CRM1-cargo recognition, release and inhibition" . Seminars in Cancer Biology . 27 : 52–61.
doi :
10.1016/j.semcancer.2014.03.002 .
ISSN
1096-3650 .
PMC
4108548 .
PMID
24631835 .
^ Research Cf (2019-12-20).
"FDA grants accelerated approval to selinexor for multiple myeloma" . FDA .
^
a
b Tickenbrock L, Cramer J, Vetter IR, Muller O (August 2002).
"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)" . J. Biol. Chem . 277 (35): 32332–8.
doi :
10.1074/jbc.M203990200 .
PMID
12070164 .
^ Ishida N, Hara T, Kamura T, Yoshida M, Nakayama K, Nakayama KI (April 2002).
"Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export" . J. Biol. Chem . 277 (17): 14355–8.
doi :
10.1074/jbc.C100762200 .
PMID
11889117 .
^ Connor MK, Kotchetkov R, Cariou S, Resch A, Lupetti R, Beniston RG, Melchior F, Hengst L, Slingerland JM (January 2003).
"CRM1/Ran-mediated nuclear export of p27(Kip1) involves a nuclear export signal and links p27 export and proteolysis" . Mol. Biol. Cell . 14 (1): 201–13.
doi :
10.1091/mbc.E02-06-0319 .
PMC
140238 .
PMID
12529437 .
^ Raval A, Weissman JD, Howcroft TK, Singer DS (January 2003).
"The GTP-binding domain of class II transactivator regulates its nuclear export" . J. Immunol . 170 (2): 922–30.
doi :
10.4049/jimmunol.170.2.922 .
PMID
12517958 .
^ Voong LN, Slater AR, Kratovac S, Cressman DE (April 2008).
"Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator" . J. Biol. Chem . 283 (14): 9031–9.
doi :
10.1074/jbc.M706487200 .
PMC
2431044 .
PMID
18245089 .
^ Thomas F, Kutay U (June 2003).
"Biogenesis and nuclear export of ribosomal subunits in higher eukaryotes depend on the CRM1 export pathway" . J. Cell Sci . 116 (Pt 12): 2409–19.
doi :
10.1242/jcs.00464 .
PMID
12724356 .
^
a
b Lindsay ME, Holaska JM, Welch K, Paschal BM, Macara IG (June 2001).
"Ran-binding protein 3 is a cofactor for Crm1-mediated nuclear protein export" . J. Cell Biol . 153 (7): 1391–402.
doi :
10.1083/jcb.153.7.1391 .
PMC
2150735 .
PMID
11425870 .
^ Kehlenbach RH, Dickmanns A, Kehlenbach A, Guan T, Gerace L (May 1999).
"A role for RanBP1 in the release of CRM1 from the nuclear pore complex in a terminal step of nuclear export" . J. Cell Biol . 145 (4): 645–57.
doi :
10.1083/jcb.145.4.645 .
PMC
2133185 .
PMID
10330396 .
^
a
b Plafker K, Macara IG (May 2000).
"Facilitated nucleocytoplasmic shuttling of the Ran binding protein RanBP1" . Mol. Cell. Biol . 20 (10): 3510–21.
doi :
10.1128/mcb.20.10.3510-3521.2000 .
PMC
85643 .
PMID
10779340 .
^ Singh BB, Patel HH, Roepman R, Schick D, Ferreira PA (Dec 1999).
"The zinc finger cluster domain of RanBP2 is a specific docking site for the nuclear export factor, exportin-1" . J. Biol. Chem . 274 (52): 37370–8.
doi :
10.1074/jbc.274.52.37370 .
hdl :
2066/120791 .
PMID
10601307 .
^ Lindsay ME, Plafker K, Smith AE, Clurman BE, Macara IG (August 2002).
"Npap60/Nup50 is a tri-stable switch that stimulates importin-alpha:beta-mediated nuclear protein import" . Cell . 110 (3): 349–60.
doi :
10.1016/s0092-8674(02)00836-x .
PMID
12176322 .
S2CID
15515037 .
^ Fornerod M, Ohno M, Yoshida M, Mattaj IW (September 1997).
"CRM1 is an export receptor for leucine-rich nuclear export signals" . Cell . 90 (6): 1051–60.
doi :
10.1016/s0092-8674(00)80371-2 .
PMID
9323133 .
S2CID
15119502 .
^ Craig E, Zhang ZK, Davies KP, Kalpana GV (January 2002).
"A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export: implications for tumorigenesis" . EMBO J . 21 (1–2): 31–42.
doi :
10.1093/emboj/21.1.31 .
PMC
125819 .
PMID
11782423 .
^ Kanai M, Hanashiro K, Kim SH, Hanai S, Boulares AH, Miwa M, Fukasawa K (September 2007). "Inhibition of Crm1-p53 interaction and nuclear export of p53 by poly(ADP-ribosyl)ation". Nat. Cell Biol . 9 (10): 1175–83.
doi :
10.1038/ncb1638 .
PMID
17891139 .
S2CID
13433567 .
^ Shao C, Lu C, Chen L, Koty PP, Cobos E, Gao W (August 2010). "p53-Dependent anticancer effects of leptomycin B on lung adenocarcinoma". Cancer Chemother. Pharmacol . 67 (6): 1369–80.
doi :
10.1007/s00280-010-1434-6 .
PMID
20803015 .
S2CID
27127578 .
Further reading
Görlich D, Kutay U (1999). "Transport between the cell nucleus and the cytoplasm". Annu. Rev. Cell Dev. Biol . 15 (1): 607–60.
doi :
10.1146/annurev.cellbio.15.1.607 .
PMID
10611974 .
Budhu AS, Wang XW (2007).
"Loading and unloading: orchestrating centrosome duplication and spindle assembly by Ran/Crm1" . Cell Cycle . 4 (11): 1510–4.
doi :
10.4161/cc.4.11.2187 .
PMC
1402358 .
PMID
16294017 .
Li L, Li HS, Pauza CD, Bukrinsky M, Zhao RY (2006).
"Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions" . Cell Res . 15 (11–12): 923–34.
doi :
10.1038/sj.cr.7290370 .
PMID
16354571 .
Stauber RH, Mann W, Knauer SK (2007).
"Nuclear and cytoplasmic survivin: molecular mechanism, prognostic, and therapeutic potential" . Cancer Res . 67 (13): 5999–6002.
doi :
10.1158/0008-5472.CAN-07-0494 .
PMID
17616652 .
Mathew C, Ghildyal R (2017).
"CRM1 inhibitors for antiviral therapy" . Frontiers in Microbiology . 8 : 1171.
doi :
10.3389/fmicb.2017.01171 .
PMC
5487384 .
PMID
28702009 .
External links