The CRM1 Nuclear Export Protein in Normal Development and Disease

摘要: CRM1 (Chromosomal Maintenance 1, also known as Exportin 1) is the major mammalian export protein that facilitates transport of large macromolecules including RNA and across nuclear membrane to cytoplasm. The gene encoding was originally identified in yeast required maintain higher order chromosome structure. In cells, found bind several pore proteins hence its role nuclear-cytosolic discovered. addition transport, plays a centrosome duplication spindle assembly, especially response DNA damage. crystal structure suggests complex binds Ran bound GTP, allowing for conformational change binding different cargo through signal (NES). Included cadre are multiple tumor suppressor oncoproteins p53, BRCA1, Survivin, NPM, APC, which function nucleus regulate transcription or aid chromosomal assembly movement. An imbalance cytosolic level these has been observed cancer resulting either inactivation (tumor suppressor) an excess anti-apoptotic activity (oncoprotein). Thus, concept inhibiting explored potential therapeutic intervention. Indeed, inhibition by variety small molecules interfere with cargo-NES results cell death. Whether all together responsible this phenotype whether specific effect unclear at time.