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

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

Authors

E Markiewicz

K Tilgner

N Barker

M van de Wetering

H Clevers

M Dorobek

I Hausmanowa-Petrusewicz

FCS Ramaekers

JLV Broers

WM Blankesteijn

G Salpingidou

RG Wilson

JA Ellis

CJ Hutchison



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.

Citation

Markiewicz, E., Tilgner, K., Barker, N., van de Wetering, M., Clevers, H., Dorobek, M., …Hutchison, C. (2006). The inner nuclear membrane protein Emerin regulates beta-catenin activity by restricting its accumulation in the nucleus. The EMBO Journal, 25(14), 3275-3285. https://doi.org/10.1038/sj.emboj.7601230

Journal Article Type Article
Publication Date Jul 1, 2006
Deposit Date May 15, 2007
Journal EMBO Journal
Print ISSN 0261-4189
Electronic ISSN 1460-2075
Publisher EMBO Press
Peer Reviewed Not Peer Reviewed
Volume 25
Issue 14
Pages 3275-3285
DOI https://doi.org/10.1038/sj.emboj.7601230
Keywords Beta-catenin, Emerin, Laminopathies, Nuclear envelope, Nuclear lamina.


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