The inner nuclear membrane protein emerin regulates beta-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 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.
Markiewicz
Ewa
E
Department of Biological Science, The School of Biological and Biomedical Sciences, The University of Durham, Durham, UK.
Tilgner
Katarzyna
K
Barker
Nick
N
van de Wetering
Mark
M
Clevers
Hans
H
Dorobek
Margareth
M
Hausmanowa-Petrusewicz
Irena
I
Ramaekers
Frans C S
FC
Broers
Jos L V
JL
Blankesteijn
W Matthijs
WM
Salpingidou
Georgia
G
Wilson
Robert G
RG
Ellis
Juliet A
JA
Hutchison
Christopher J
CJ
D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000378:metabolism; D009685:Nuclear Envelope / Q000502:physiology*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013946:Thymopoietins / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D008565:Membrane Proteins; D009687:Nuclear Proteins; D013946:Thymopoietins; D015534:Trans-Activators; D051176:beta Catenin; C092710:emerin