Cited by 246Nuclear Structure and FunctionWnt/β-catenin signaling in development and cancerConnexins and lens biology

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

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Markiewicz, Ewa, Tilgner, Katarzyna, Barker, Nick, van de Wetering, Mark, Clevers, Hans, Dorobek, Margareth, Hausmanowa‐Petrusewicz, Irena, Ramaekers, Frans CS +6 more·2006·The EMBO Journal

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 beta-catenin, an important transcription coactivator, into the nucleus. Emerin interacts with beta-catenin through a conserved adenomatous polyposis coli (APC)-like domain. When GFP-emerin is expressed in HEK293 cells, beta-catenin is restricted to the cytoplasm and beta-catenin activity is inhibited. In contrast, expression of an emerin mutant, lacking its APC-like domain (GFP-emerinDelta), dominantly stimulates beta-catenin activity and increases nuclear accumulation of beta-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 beta-catenin and can be replicated in wild-type fibroblasts by transfection with constitutively active beta-catenin. Our results support recent findings that suggest that INM proteins can influence signalling pathways by restricting access of transcription coactivators to the nucleus.

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Authors
Markiewicz, E., Tilgner, K., Barker, N., van de Wetering, M., Clevers, H., Dorobek, M., Hausmanowa‐Petrusewicz, I., Ramaekers, F. C., Broers, J. L., Blankesteijn, W. M., Salpingidou, G., Wilson, R. G., Ellis, J. A., & Hutchison, C. J.
Affiliations
  • Durham University (GB)
  • Hubrecht Institute for Developmental Biology and Stem Cell Research (NL)
  • Polish Academy of Sciences (PL)
  • Maastricht University (NL)
  • James Cook University Hospital (GB)
  • King's College London (GB)
Corresponding author
Hutchison, Christopher J
Venue
The EMBO Journal
Published
2006-07-20
Volume
25
Issue
14
Pages
3275-3285
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W2115754063
Cited by
246
References
57
Citations by year
2026: 8 · 2025: 8 · 2024: 6 · 2023: 5 · 2022: 10 · 2021: 10 · 2020: 15 · 2019: 10 · 2018: 13 · 2017: 12 · 2016: 17 · 2015: 16 · 2014: 18 · 2013: 13 · 2012: 17
FWCI
5.71
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • TU/e Research Portal (publishedVersion)
  • Durham Research Online (Durham University) (acceptedVersion)
  • TU/e Research Portal (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Durham Research Online (Durham University) (submittedVersion)
  • Durham Research Online (Durham University) (submittedVersion, cc-by)
  • Research Portal (King's College London) (submittedVersion)
  • KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
  • Wellcome Trust
  • Royal Society
  • Muscular Dystrophy UK
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
Keywords
emerin, inner nuclear membrane, β-catenin, nuclear accumulation, transcriptional coactivator, nuclear trafficking, Wnt signaling
MeSH terms
Cell Line, Cells, Cultured, Humans, Membrane Proteins, Nuclear Envelope, Nuclear Proteins, Thymopoietins, Signal Transduction, Trans-Activators, Muscular Dystrophy, Emery-Dreifuss, beta Catenin

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