The nuclear pore complex (NPC) mediates trafficking between the cytoplasm and nucleoplasm. It also plays key roles in other nuclear processes such as
chromatin silencing, transcriptional regulation, and DNA damage repair.
Nucleoporins, the structural components of the NPC, have been linked to a multitude of
cancers through
chromosomal translocations generating fusion
proteins, changes in
protein expression levels, and single point mutations. Only a small number of
nucleoporins have been linked to
tumorigenesis thus far, and these proteins--Nup62, Nup88,
Nup98, Nup214, Nup358/
RanBP2, and Tpr--line the trafficking pathway and are particularly associated with
mRNA export. Overexpression of several associated nuclear export factors, most also involved in various stages of
mRNA export, has been linked to
cancers as well. Some oncogenic
nucleoporin mutants are mislocalized to either the cytoplasm or nucleoplasm while others are incorporated into the NPC, and in all these cases they are thought to misregulate signaling pathways and transcription through either altered or diminished
nucleoporin functionality. Intriguingly, many viruses target the same
cancer-linked
nucleoporins, often causing their degradation or mislocalization, implying that these viruses exploit some of the same weaknesses as the oncogenic defects.