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

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 β‐catenin, an important tra...

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Bibliographic Details
Published in:The EMBO journal 2006-07, Vol.25 (14), p.3275-3285
Main Authors: Markiewicz, Ewa, Tilgner, Katarzyna, Barker, Nick, van de Wetering, Mark, Clevers, Hans, Dorobek, Margareth, Hausmanowa-Petrusewicz, Irena, Ramaekers, Frans CS, Broers, Jos LV, Blankesteijn, W Matthijs, Salpingidou, Georgia, Wilson, Robert G, Ellis, Juliet A, Hutchison, Christopher J
Format: Article
Language:English
Subjects:
beta Catenin - antagonists & inhibitors
beta Catenin - metabolism
Cell Line
Cells, Cultured
emerin
Humans
laminopathies
Membrane Proteins - physiology
Muscular Dystrophy, Emery-Dreifuss - metabolism
nuclear envelope
Nuclear Envelope - physiology
nuclear lamina
Nuclear Proteins - antagonists & inhibitors
Nuclear Proteins - metabolism
Signal Transduction - physiology
Thymopoietins - physiology
Trans-Activators - physiology
β-Catenin
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Summary: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 β‐catenin, an important transcription coactivator, into the nucleus. Emerin interacts with β‐catenin through a conserved adenomatous polyposis coli (APC)‐like domain. When GFP‐emerin is expressed in HEK293 cells, β‐catenin is restricted to the cytoplasm and β‐catenin activity is inhibited. In contrast, expression of an emerin mutant, lacking its APC‐like domain (GFP‐emerinΔ), dominantly stimulates β‐catenin activity and increases nuclear accumulation of β‐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 β‐catenin and can be replicated in wild‐type fibroblasts by transfection with constitutively active β‐catenin. Our results support recent findings that suggest that INM proteins can influence signalling pathways by restricting access of transcription coactivators to the nucleus.
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7601230