title: Atomic basis of CRM1-cargo recognition, release and inhibition.
abstract: CRM1 or XPO1 is the major nuclear export receptor in the cell, which controls the nuclear-cytoplasmic localization of many proteins and RNAs. CRM1 is also a promising cancer drug target as the transport receptor is overexpressed in many cancers where some of its cargos are misregulated and mislocalized to the cytoplasm. Atomic level understanding of CRM1 function has greatly facilitated recent drug discovery and development of CRM1 inhibitors to target a variety of malignancies. Numerous atomic resolution CRM1 structures are now available, explaining how the exporter recognizes nuclear export signals in its cargos, how RanGTP and cargo bind with positive cooperativity, how RanBP1 causes release of export cargos in the cytoplasm and how diverse inhibitors such as Leptomycin B and the new KPT-SINE compounds block nuclear export. This review summarizes structure-function studies that explain CRM1-cargo recognition, release and inhibition.
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, TX 75390-9041, USA. Electronic address: HoYeeJoyce.Fung@UTSouthwestern.edu.
authors.forename: Ho Yee Joyce
authors.initials: HY
authors.lastname: Fung
authors.affiliation: Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, TX 75390-9041, USA. Electronic address: YuhMin.Chook@UTSouthwestern.edu.
authors.forename: Yuh Min
authors.initials: YM
authors.lastname: Chook
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D028884:Karyopherins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D020931:ran GTP-Binding Protein / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D002352:Carrier Proteins; D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein
keywords: Exportin; Karyopherin; NES; Nuclear export; Nuclear pore complex