TAILIEUCHUNG - Báo cáo khoa học: The monopartite nuclear localization signal of autoimmune regulator mediates its nuclear import and interaction with multiple importin a molecules

Autoimmune regulator (AIRE) is a transcriptional regulator involved in establishing immunological self-tolerance. Mutations in theAIREgene lead to the development of the autosomal, recessively inherited, organ-specific autoimmune disease, autoimmune polyendocrinopathy candidiasis ectoder-mal dystrophy (APECED). | ềFEBS Journal The monopartite nuclear localization signal of autoimmune regulator mediates its nuclear import and interaction with multiple importin a molecules Tanja Ilmarinen1 Krister Melen2 Hannele Kangas1 Ilkka Julkunen2 Ismo Ulmanen1 and Petra Eskelin1 3 1 Department of Molecular Medicine National public Health Institute Helsinki Finland 2 Department of ViralDiseases and Immunology NationalPublic Health Institute Helsinki Finland 3 Hospitalfor Children and Adolescents Helsinki University Hospital Helsinki Finland Keywords autoimmune regulator AIRE importin a karyopherin a nuclear import Correspondence T. Ilmarinen NationalPublic Health Institute Department of Molecular Medicine Biomedicum Helsinki Haartmaninkatu 8 00290 Helsinki Finland Fax 358 9 4744 8480 Tel 358 9 4744 8275 E-mail Received 6 September 2005 revised 31 October 2005 accepted 17 November 2005 doi Autoimmune regulator AIRE is a transcriptional regulator involved in establishing immunological self-tolerance. Mutations in the AIRE gene lead to the development of the autosomal recessively inherited organ-specific autoimmune disease autoimmune polyendocrinopathy candidiasis ectodermal dystrophy APECED . The AIRE protein is mainly localized in the cell nucleus where it is associated with nuclear bodies. The N-terminal part of AIRE has been previously shown to mediate nuclear localization of the protein. However the functional nuclear localization signal NLS and nuclear import mechanisms of AIRE have not been identified. We show that although the amino-acid sequence of AIRE contains a potential bipartite NLS consisting of amino acids 110-114 and 131-133 only the latter part constitutes a functional NLS. Furthermore we show by in vitro binding assays that AIRE interacts with multiple members of the nuclear transport receptor importin a family mainly a1 a3 and a5 and that these interactions depend on the intactness of the Arg-Lys-rich NLS of AIRE. .

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