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CRM1

CRM1 is present in all eukaryotic cells and was initially identified as a chromosomal mutation in the yeast schizosaccharomyces pombe. Also known as exportin 1 or XPO1, it is responsible for the transport of over 200 proteins, which include many tumor suppressor proteins (TSP) and oncoproteins. CRM1 plays an essential role in mitosis through (I) binding and targeting key mitotic proteins to specific areas of the mitotic spindle; and (II) stabilizing the microtubule kinetochore to promote proper chromosomal segregation. Inhibition of RCC1, which regulates CRM1, by actinomycin D resulted in severe spindle assembly defects and mitotic catastrophe. Among the list of CRM1-mediated proteins are p53, FOXOs, p27, nucleophosmin, BCR-ABL, p21, PI3K/AKT, Wnt/β-catenin, NF-kB, APC, and Rb, all of which are significant targets in oncogenesis. Dysregulation of this transport process has been implicated in cancer, in addition to wound healing, inflammation, and viral infections. CRM1 overexpression has been demonstrated in both solid tumors and hematologic malignancies, and this overexpression is associated with a poorer prognosis and drug resistance. The exact mechanism by which this occurs remains unclear but is thought to involve altered transport mechanisms in favor of cytoplasmic localization and the modification of nuclear proteins to reveal their LR-NES enabling them to bind CRM1.

References

1.Amy Y. Wang,et al. Stem Cell Investig. 2019; 6: 6.

Membrane Transporter/Ion Channel

AMPK(52) ASBT Transporter(6) BCRP(9) Beta Amyloid(26) Carbonic Anhydrase(25) Chloride Channel(29) CRAC Channel(3) CRM1(4) Exportin-1(5) FABP(4) GAT(62) GLUT(5) Glutamate Transporter(1) GlyT(10) HCN Channel(4) iGluR(33) Monoamine Transporter(19) Monocarboxylate Transporter(7) MTP(1) nAChR(5) NADPH(25) Na-K-ATPase(1) NKCC(4) NMDAR(45) OCT(4) Other Targets(13) P2X Receptor(16) P-glycoprotein(10) Proton Pump(33) Sodium Channel(103) TRP/TRPV Channel(92) URAT1(1)