Exportin 1 (XPO1) (XPO1)

Exportin 1 (XPO1), also known as Chromosome Region Maintenance 1 (CRM1), is a critical nuclear export receptor belonging to the karyopherin-beta family. It facilitates the transport of over 200 cargo proteins and several RNA species from the nucleus to the cytoplasm by recognizing leucine-rich nuclear export signals (NES) (UniProt O14980). Among its key cargoes are essential tumor suppressor proteins (TSPs) such as p53, BRCA1, and p21, which regulate cell cycle progression and apoptosis (Gravina et al., Seminars in Cancer Biology, 2014). In many malignancies, XPO1 is frequently overexpressed, leading to the aberrant export and subsequent inactivation of these TSPs, thereby promoting uncontrolled cell growth and survival (Wang et al., J Hematol Oncol, 2019). Therapeutic targeting of XPO1 involves Selective Inhibitor of Nuclear Export (SINE) compounds, such as the FDA-approved drug selinexor. These small molecules work by covalently binding to the Cys528 residue within the XPO1 cargo-binding pocket, effectively blocking the export of TSPs (Kim et al., Drugs of Today, 2020). This inhibition results in the nuclear accumulation and reactivation of tumor suppressors, which induces apoptosis specifically in neoplastic cells while sparing normal cells (Sun et al., Signal Transduction and Targeted Therapy, 2016).

Other names

Chromosome region maintenance 1 proteinCRM1Exp1Exportin-1

Selective inhibition of nuclear export (SINE) via covalent binding to the Cys528 residue in the NES-binding pocket (Wang et al., J Hematol Oncol, 2019).