Nuclear pore complex protein Nup98 (NUP98) (NUP98)

Nuclear pore complex protein Nup98 (NUP98) is a versatile component of the nuclear pore complex (NPC) that facilitates the bidirectional transport of macromolecules between the nucleus and cytoplasm [1.2.1, 1.4.2]. Beyond its role at the NPC, NUP98 acts as a mobile transcriptional regulator that associates with chromatin and co-activators like CBP/p300 to modulate gene expression [1.3.1, 1.3.4]. In clinical medicine, NUP98 is primarily recognized for its involvement in chromosomal translocations that generate oncogenic fusion proteins, such as NUP98-NSD1 and NUP98-KDM5A, which are hallmarks of high-risk pediatric acute myeloid leukemia (AML) [1.2.1, 1.5.1]. These fusions drive malignancy by aberrantly activating the HOXA/MEIS1 transcriptional program and disrupting normal epigenetic control [1.2.2, 1.3.4]. Therapeutic targeting of NUP98-rearranged cancers focuses on disrupting these oncogenic pathways, notably through the use of menin inhibitors to block the Menin-MLL interaction and XPO1 inhibitors to arrest aberrant nuclear export [1.2.2, 1.3.4]. Additionally, NUP98 is exploited by various viruses, including SARS-CoV-2 and HIV-1, to subvert host cell transport mechanisms [1.4.2]. Despite emerging targeted therapies, NUP98-rearranged leukemias remain difficult to treat due to their association with primary induction failure and poor overall survival [1.5.2, 1.5.3].

Other names

NUP98Nucleoporin 9898 kDa nucleoporinAVDNuclear pore complex protein Nup98-Nup96

Inhibition of the Menin-MLL interaction to downregulate HOXA and MEIS1 gene expression, and inhibition of XPO1-mediated nuclear export of oncogenic factors [1.2.2, 1.3.4].