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

Ewa Markiewicz, Katarzyna Tilgner, Nick Barker, Mark Van De Wetering, Hans Clevers, Margareth Dorobek, Irena Hausmanowa-Petrusewicz, Frans C.S. Ramaekers, Jos L.V. Broers, W. Matthijs Blankesteijn, Georgia Salpingidou, Robert G. Wilson, Juliet A. Ellis, Christopher J. Hutchison

Research output: Contribution to journalArticlepeer-review

201 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)3275-3285
Number of pages11
JournalEMBO Journal
Volume25
Issue number14
DOIs
Publication statusPublished - 26 Jul 2006
Externally publishedYes

Keywords

  • Emerin
  • Laminopathies
  • Nuclear envelope
  • Nuclear lamina
  • β-Catenin

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