Nuclear pore complex (NPC) (NPC)

The nuclear pore complex (NPC) is a massive, multi-protein assembly embedded within the nuclear envelope that serves as the primary gateway for all macromolecular exchange between the nucleus and the cytoplasm [11, 12, 16]. It is composed of approximately 30 distinct proteins known as nucleoporins (Nups) arranged in a highly organized, eight-fold symmetrical channel that regulates the selective transport of RNA, proteins, and signaling molecules while maintaining nuclear integrity [12, 19, 22]. In oncogenesis, the NPC is frequently dysregulated through the overexpression of specific Nups or the formation of chimeric fusion proteins, which can lead to the aberrant sequestration of tumor suppressors or the excessive export of growth-promoting factors [3, 8, 9, 14]. Structural defects in the NPC and the resulting failure of nucleocytoplasmic transport are also central to the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia, and Alzheimer’s disease, often linked to the cytoplasmic aggregation of proteins like TDP-43 [7, 11, 21]. Clinically, the transport machinery within the NPC is targeted by Selective Inhibitor of Nuclear Export (SINE) compounds like Selinexor, which inhibit the XPO1 receptor [3, 8, 18]. Emerging therapeutic strategies are exploring the direct inhibition of NPC assembly or the targeting of specific Nup interactions to selectively induce apoptosis in rapidly proliferating cancer cells while sparing non-dividing healthy cells [2, 23].

Other names

Nuclear poreNucleoporin complexNuclear nanoporeNucleoporin assembly

Selective inhibition of nuclear export (SINE) via XPO1 blockade, disruption of NPC assembly by targeting scaffold nucleoporins (e.g., NUP93, NDC1), inhibition of specific nucleoporin-transport receptor interactions, and modulation of the phase separation (LLPS) of phenylalanine-glycine (FG) repeats within the central channel [2, 3, 5, 22, 23].