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The inner nuclear membrane protein Emerin regulates β‐catenin activity by restricting its accumulation in the nucleus
Author(s) -
Markiewicz Ewa,
Tilgner Katarzyna,
Barker Nick,
van de Wetering Mark,
Clevers Hans,
Dorobek Margareth,
HausmanowaPetrusewicz Irena,
Ramaekers Frans CS,
Broers Jos LV,
Blankesteijn W Matthijs,
Salpingidou Georgia,
Wilson Robert G,
Ellis Juliet A,
Hutchison Christopher J
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601230
Subject(s) - emerin , biology , microbiology and biotechnology , cytoplasm , coactivator , nuclear protein , beta catenin , transfection , inner membrane , nuclear localization sequence , transcription factor , genetics , wnt signaling pathway , gene , signal transduction , mitochondrion
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.