title: Diversification of importin-α isoforms in cellular trafficking and disease states.
abstract: The human genome encodes seven isoforms of importin α which are grouped into three subfamilies known as α1, α2 and α3. All isoforms share a fundamentally conserved architecture that consists of an N-terminal, autoinhibitory, importin-β-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-α isoforms display remarkable substrate specificity in vivo. In the present review, we look at key differences among importin-α 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 α into seven isoforms expands the dynamic range and regulatory control of nucleocytoplasmic transport, offering unexpected opportunities for pharmacological intervention. The emerging view of importin α 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.
authors: *Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, U.S.A.
authors: Ruth A
authors: RA
authors: Pumroy
authors: *Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, U.S.A.
authors: Gino
authors: G
authors: Cingolani
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism* / Q000821:virology; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D008958:Models, Molecular; D019913:Nuclear Localization Signals; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015398:Signal Transduction; D014764:Viral Proteins / Q000378:metabolism*; D014777:Virus Diseases / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019913:Nuclear Localization Signals; D020033:Protein Isoforms; D014764:Viral Proteins; D028901:alpha Karyopherins
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