Diversification of importin-? isoforms in cellular trafficking and disease states.

ABSTRACT: The human genome encodes seven isoforms of importin ? which are grouped into three subfamilies known as ?1, ?2 and ?3. All isoforms share a fundamentally conserved architecture that consists of an N-terminal, autoinhibitory, importin-?-binding (IBB) domain and a C-terminal Arm (Armadillo)-core that associates with nuclear localization signal (NLS) cargoes. Despite striking similarity in amino acid sequence and 3D structure, importin-? isoforms display remarkable substrate specificity in vivo. In the present review, we look at key differences among importin-? isoforms and provide a comprehensive inventory of known viral and cellular cargoes that have been shown to associate preferentially with specific isoforms. We illustrate how the diversification of the adaptor importin ? into seven isoforms expands the dynamic range and regulatory control of nucleocytoplasmic transport, offering unexpected opportunities for pharmacological intervention. The emerging view of importin ? is that of a key signalling molecule, with isoforms that confer preferential nuclear entry and spatiotemporal specificity on viral and cellular cargoes directly linked to human diseases.

SUBMITTER: Pumroy RA 

PROVIDER: S-EPMC4405237 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature