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

Markiewicz, E. and Tilgner, K. and Barker, N. and van de Wetering, M. and Clevers, H. and Dorobek, M. and Hausmanowa-Petrusewicz, I. and Ramaekers, F. C. S. and Broers, J. L. V. and Blankesteijn, W. M. and Salpingidou, G. and Wilson, R. G. and Ellis, J. A. and Hutchison, C. J. (2006) 'The inner nuclear membrane protein Emerin regulates beta-catenin activity by restricting its accumulation in the nucleus.', EMBO journal., 25 (14). pp. 3275-3285.

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.

Item Type:Article
Keywords:Beta-catenin, Emerin, Laminopathies, Nuclear envelope, Nuclear lamina.
Full text:Full text not available from this repository.
Publisher Web site:http://dx.doi.org/10.1038/sj.emboj.7601230
Record Created:15 May 2007
Last Modified:08 Apr 2009 16:31

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