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The inner nuclear membrane protein Emerin regulates beta-cateninactivity by restricting its accumulation in the nucleus

Lookup NU author(s): Dr Katarzyna Tilgner, Professor Christopher Hutchison

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Abstract

Emerin is a type II inner nuclear membrane (INM) protein of unknown function. Emerin function is likely to be important because, when it is mutated, emerin promotes both skeletal muscle and heart defects. Here we show that one function of Emerin is to regulate the flux of -catenin, an important transcription coactivator, into the nucleus. Emerin interacts with -catenin through a conserved adenomatous polyposis coli (APC)-like domain. When GFP-emerin is expressed in HEK293 cells, -catenin is restricted to the cytoplasm and -catenin activity is inhibited. In contrast, expression of an emerin mutant, lacking its APC-like domain (GFP-emerin), dominantly stimulates -catenin activity and increases nuclear accumulation of -catenin. Human fibroblasts that are null for emerin have an autostimulatory growth phenotype. This unusual growth phenotype arises through enhanced nuclear accumulation and activity of -catenin and can be replicated in wild-type fibroblasts by transfection with constitutively active -catenin. Our results support recent findings that suggest that INM proteins can influence signalling pathways by restricting access of transcription coactivators to the nucleus.


Publication metadata

Author(s): Markiewicz E, Tilgner K, Barker N, van de Wetering M, Clevers H, Dorobek M, Hausmanowa-Petrusewicz I, Ramaekers FCS, Broers JLV, Blankesteijn WM, Salpingidou G, Wilson RG, Ellis JA, Hutchison CJ

Publication type: Article

Publication status: Published

Journal: EMBO Journal

Year: 2007

Volume: 25

Issue: 14

Pages: 3275-3285

ISSN (print): 0261-4189

ISSN (electronic): 1460-2075

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/sj.emboj.7601230

DOI: 10.1038/sj.emboj.7601230


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