Exportin-1

CRM1 is present in all eukaryotic cells, 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.

References

1.Wang AY,et al. Stem Cell Investig. 2019;6:6. Published 2019 Feb 25.