Importin (IMP)

Importins, also known as nuclear import proteins or karyopherins, are a superfamily of transport receptors that mediate the movement of proteins and RNAs from the cytoplasm into the nucleus [4, 9]. They are essential for maintaining cellular homeostasis by regulating the nuclear entry of transcription factors, cell cycle regulators, and signaling molecules [2, 14]. In various cancers, such as melanoma and breast cancer, these proteins are frequently overexpressed, leading to the aberrant nuclear localization of oncogenic factors and the suppression of tumor suppressors [1, 3]. Furthermore, many viruses, including HIV-1, Influenza, and SARS-CoV-2, exploit the host's nuclear import machinery to transport their genetic material and proteins into the nucleus for replication [7, 13]. Drugs targeting these proteins, such as ivermectin and importazole, act by inhibiting the interaction between the importin and its cargo or by disrupting the RanGTP-dependent transport cycle [5, 10]. While these inhibitors show potential as anticancer and antiviral agents in preclinical studies, their clinical application is challenged by the risk of systemic toxicity due to the fundamental role of nuclear transport in all eukaryotic cells [3, 11].

Other names

KaryopherinNuclear import receptorNuclear transport receptorTransportinNTRKaryopherin-betaKaryopherin-alpha

Inhibition of the interaction between nuclear import receptors (importins) and their cargo proteins containing nuclear localization signals (NLS), or disruption of the RanGTP-mediated cargo release mechanism, thereby preventing the nuclear entry of essential host or viral proteins [5, 7, 10].