Exportin-1 (XPO1) receptor (XPO1)

Exportin-1 (XPO1), also known as Chromosome Region Maintenance 1 (CRM1), is a critical nuclear export receptor belonging to the karyopherin beta family [UniProt]. It mediates the transport of over 200 cargo proteins, including tumor suppressor proteins (TSPs) such as p53, p21, and BRCA1, from the nucleus to the cytoplasm [PubMed: 30104729]. In many cancers, XPO1 is overexpressed, leading to the excessive export and subsequent inactivation of these TSPs in the cytoplasm, which promotes uncontrolled cell proliferation and survival [StatPearls]. Therapeutic targeting of XPO1 with Selective Inhibitors of Nuclear Export (SINE), such as selinexor, forces the nuclear retention and reactivation of these tumor suppressors, inducing apoptosis in malignant cells while sparing normal cells [FDA]. This mechanism has proven effective in treating hematologic malignancies like multiple myeloma and diffuse large B-cell lymphoma, and is currently being explored in various solid tumors [NCI].

Other names

CRM1Chromosome region maintenance 1Exp1Exportin 1

Selective inhibition of nuclear export (SINE) via covalent binding to the cysteine 528 residue in the cargo-binding pocket of XPO1, preventing the export of tumor suppressor proteins and other regulatory factors [PubMed: 29335501].