Nucleoporin genes in human diseases

Abstract

Nuclear pore complexes (NPCs) are large channels spanning the nuclear envelope that mediate nucleocytoplasmic transport. They are composed of multiple copies of ~30 proteins termed nucleoporins (NUPs). Alterations in NUP genes are linked to several human neoplastic and non-neoplastic diseases. This review focuses on NUPs, their genes, localization, function in the NPC and involvement in human diseases.

Figure 1

Schematic representation of a nucleus with external and internal view of NPCs. Each NUP group is represented by a different color: orange, transmembrane NUPs; blue, coat NUPs; yellow, adapter NUPs; pink, channel NUPs; violet, nuclear basket NUPs; brown, cytoplasmic filament NUPs.

Figure 2

Promiscuous NUP genes. (a) TPR fusion partner genes and their chromosomal localization. (b) In all fusions TPR N-terminal coiled-coil domain is maintained and fused to the partner kinase domain. (c) RANBP2 partner genes and their chromosomal localization. (d) In all fusion proteins RANBP2 N-terminal leucine-rich domain is retained and fused with the tyrosine kinase domain of the partner gene. (e) NUP214 fusion partner genes and their chromosomal localization. (f) Both DEK-NUP214 and SET-NUP214 join DEK or SET protein to the C-terminal two-thirds of NUP214, including a portion of the coiled-coil domain and the FG repeat domain. Similarly NUP214-SQSTM1 chimeric protein fuses N-terminal half of SQSTM1 with a small portion of NUP214 FG repeats domain. Instead NUP214-ABL1 is composed of the N terminus of NUP214, including its β-propeller, coiled-coil domain and FG repeats, fused with most of the ABL1 tyrosine kinase protein. (g) Homeodomain (HD, blue) and non-HD (black) NUP98 fusion partner genes and their chromosomal localization. (h) In all fusion proteins NUP98 preserves GLFG repeats and GLE2-binding domain (GBD), fused with the C-terminal portion of partner genes.