XPO1

XPO1
XPO1
사용 가능한 구조물
PDB직교 검색: PDBe RCSB
식별자
별칭XPO1, CRM1, emb, exp1, exportin 1, CRM-1
외부 IDOMIM: 602559 MGI: 2144013 호몰로진: 2554 GeneCard: XPO1
직교체
종인간마우스
엔트레스

7514

103573

앙상블

ENSG000082898

ENSMUSG00000020290

유니프로트

O14980

Q6P5F9

RefSeq(mRNA)

NM_003400

NM_001035226
NM_134014

RefSeq(단백질)

NP_003391

NP_001030303
NP_598775

위치(UCSC)Chr 2: 61.48 – 61.54MbChr 11: 23.21 – 23.25Mb
PubMed 검색[3][4]
위키다타
인간 보기/편집마우스 보기/편집

염색체 부위 유지 1(CRM1)이라고도 알려진 엑스포딘 1(XPO1)은 다양한 단백질과 RNA의 핵 수출을 매개하는 진핵 단백질이다.

역사

XPO1(CRM1)은 원래 유전자 화면에서 핵분열 효모인 정신분열효모세포 퐁베에서 확인되었으며, 조사자들은 염색체 구조의 통제에 관여한다고 판단했다.[5]이후 루신이 풍부한 핵수출신호(NES)를 탑재한 카고용 핵수송수용체임이 드러났다.[6][7][8][9]XPO1과 카고와의 상호작용에 대한 구조적 세부사항은 유전자가 확인된 지 20년 만에 밝혀졌다.[10][11][12][13]

함수

XPO1은 NES 의존성 단백질 수송을 매개한다.그것은 핵으로부터 수 백개의 다른 단백질을 수출한다.[14][15] XPO1은 리보솜 서브유닛의 핵 수출에 관여한다.[16][17][18] XPO1은 U snRNA, rRNA, 그리고 일부 mRNA를 포함한 다양한 RNA의 수출에 역할을 한다.[19][20][21]

의료 관련성

XPO1은 다양한 바이러스 감염에 관련되어 있다.예를 들어, 감염 주기의 중요한 부분인 바이러스성 단백질 Rev와 함께 복합적으로 HIV-1 RNA의 핵 수출에 필요하다.[22] XPO1은 일부 암 유형에 영향을 받아 항암제 개발 대상으로 간주된다.[24]Selinexor는 XPO1을 특별히 목표로 하는 약물로서, 다발성 골수종 치료로 FDA로부터 승인을 받았다.[25]

상호작용

XPO1은 다음과 상호 작용하는 것으로 나타났다.

참고 항목

참조

  1. ^ a b c GRCh38: 앙상블 릴리스 89: ENSG000082898 - 앙상블, 2017년 5월
  2. ^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG000020290 - 앙상블, 2017년 5월
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ Fornerod, M.; Ohno, M.; Yoshida, M.; Mattaj, I. W. (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.
  7. ^ 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. doi:10.1038/36894. ISSN 0028-0836. PMID 9384386.
  8. ^ Stade, K.; Ford, C. S.; 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.
  9. ^ 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.
  10. ^ Monecke, Thomas; Güttler, Thomas; Neumann, Piotr; Dickmanns, Achim; Görlich, Dirk; Ficner, Ralf (2009-05-22). "Crystal structure of the nuclear export receptor CRM1 in complex with Snurportin1 and RanGTP". Science. 324 (5930): 1087–1091. doi:10.1126/science.1173388. ISSN 1095-9203. PMID 19389996.
  11. ^ Dong, Xiuhua; Biswas, Anindita; Süel, Katherine E.; Jackson, Laurie K.; Martinez, Rita; Gu, Hongmei; Chook, Yuh Min (2009-04-30). "Structural basis for leucine-rich nuclear export signal recognition by CRM1". Nature. 458 (7242): 1136–1141. doi:10.1038/nature07975. ISSN 1476-4687. PMC 3437623. PMID 19339969.
  12. ^ Dong, Xiuhua; Biswas, Anindita; Chook, Yuh Min (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.
  13. ^ Güttler, Thomas; Madl, Tobias; Neumann, Piotr; Deichsel, Danilo; Corsini, Lorenzo; Monecke, Thomas; Ficner, Ralf; Sattler, Michael; Görlich, Dirk (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.
  14. ^ Thakar, Ketan; Karaca, Samir; Port, Sarah A.; Urlaub, Henning; Kehlenbach, Ralph H. (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.
  15. ^ Kırlı, Koray; Karaca, Samir; Dehne, Heinz Jürgen; Samwer, Matthias; Pan, Kuan Ting; Lenz, Christof; Urlaub, Henning; Görlich, Dirk (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.
  16. ^ Moy, T. I.; Silver, P. A. (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.
  17. ^ Ho, J. H.; Kallstrom, G.; Johnson, A. W. (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.
  18. ^ Zemp, Ivo; Wild, Thomas; O'Donohue, Marie-Françoise; Wandrey, Franziska; Widmann, Barbara; Gleizes, Pierre-Emmanuel; Kutay, Ulrike (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.
  19. ^ Cullen, B. R. (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.
  20. ^ Köhler, Alwin; Hurt, Ed (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.
  21. ^ "Nucleocytoplasmic Transport of RNAs and RNA–Protein Complexes". Journal of Molecular Biology. 428 (10): 2040–2059. 2016-05-22. doi:10.1016/j.jmb.2015.09.023. ISSN 0022-2836.
  22. ^ Booth, David S; Cheng, Yifan; Frankel, Alan D (2014-12-08). Sundquist, Wesley I (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. PMID 25486595.
  23. ^ Taylor, Justin; Sendino, Maria; Gorelick, Alexander N.; Pastore, Alessandro; Chang, Matthew T.; Penson, Alexander V.; Gavrila, Elena I.; Stewart, Connor; Melnik, Ella M.; Herrejon Chavez, Florisela; Bitner, Lillian (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.
  24. ^ Fung, Ho Yee Joyce; Chook, Yuh Min (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.
  25. ^ Research, Center for Drug Evaluation and (2019-12-20). "FDA grants accelerated approval to selinexor for multiple myeloma". FDA.
  26. ^ 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.
  27. ^ 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.
  28. ^ 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.
  29. ^ 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.
  30. ^ 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.
  31. ^ 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.
  32. ^ 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.
  33. ^ 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.
  34. ^ 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.
  35. ^ 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. PMID 10601307.
  36. ^ 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.
  37. ^ 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.
  38. ^ 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.
  39. ^ 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.
  40. ^ 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.

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인간 염색체 2의 유전자에 관한 이 기사는 단조롭다.위키피디아를 확장하여 도울 수 있다.