TGF-β signalling is regulated by Schnurri-2 dependent nuclear translocation of CLIC4 and consequent stabilization of phospho Smad2–3

CLIC4, a multifunctional protein that traffics between the cytoplasm and nucleus, interacts with Schnurri-2, a transcription factor in the BMP pathway. TGF-β enhances the expression of both CLIC4 and Schnurri-2 and promotes their association in the cytoplasm and their translocation to the nucleus. I...

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Autores principales: Shukla, Anjali, Malik, Mariam, Cataisson, Christophe, Ho, Yan, Friesen, Travis, Suh, Kwang S., Yuspa, Stuart H.
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825893/
https://www.ncbi.nlm.nih.gov/pubmed/19448624
http://dx.doi.org/10.1038/ncb1885
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author Shukla, Anjali
Malik, Mariam
Cataisson, Christophe
Ho, Yan
Friesen, Travis
Suh, Kwang S.
Yuspa, Stuart H.
author_facet Shukla, Anjali
Malik, Mariam
Cataisson, Christophe
Ho, Yan
Friesen, Travis
Suh, Kwang S.
Yuspa, Stuart H.
author_sort Shukla, Anjali
collection PubMed
description CLIC4, a multifunctional protein that traffics between the cytoplasm and nucleus, interacts with Schnurri-2, a transcription factor in the BMP pathway. TGF-β enhances the expression of both CLIC4 and Schnurri-2 and promotes their association in the cytoplasm and their translocation to the nucleus. In the absence of CLIC4 or Schnurri-2, TGF-β signalling is abrogated. Direct nuclear targeting of CLIC4 enhances TGF-β signalling and removes the requirement for Schnurri-2. Nuclear CLIC4 associates with phospho-Smad2 and 3 and protects them from dephosphorylation by nuclear phosphatases. An intact TGF-β signalling pathway is essential for CLIC4 to mediate growth arrest. These results reveal Schnurri-2 and CLIC4 as previously unidentified modifiers of TGF-β signalling through stabilizing phospho-Smad2 and phospho-Smad3 in the nucleus.
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spelling pubmed-28258932010-02-22 TGF-β signalling is regulated by Schnurri-2 dependent nuclear translocation of CLIC4 and consequent stabilization of phospho Smad2–3 Shukla, Anjali Malik, Mariam Cataisson, Christophe Ho, Yan Friesen, Travis Suh, Kwang S. Yuspa, Stuart H. Nat Cell Biol Article CLIC4, a multifunctional protein that traffics between the cytoplasm and nucleus, interacts with Schnurri-2, a transcription factor in the BMP pathway. TGF-β enhances the expression of both CLIC4 and Schnurri-2 and promotes their association in the cytoplasm and their translocation to the nucleus. In the absence of CLIC4 or Schnurri-2, TGF-β signalling is abrogated. Direct nuclear targeting of CLIC4 enhances TGF-β signalling and removes the requirement for Schnurri-2. Nuclear CLIC4 associates with phospho-Smad2 and 3 and protects them from dephosphorylation by nuclear phosphatases. An intact TGF-β signalling pathway is essential for CLIC4 to mediate growth arrest. These results reveal Schnurri-2 and CLIC4 as previously unidentified modifiers of TGF-β signalling through stabilizing phospho-Smad2 and phospho-Smad3 in the nucleus. 2009-05-17 2009-06 /pmc/articles/PMC2825893/ /pubmed/19448624 http://dx.doi.org/10.1038/ncb1885 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Shukla, Anjali
Malik, Mariam
Cataisson, Christophe
Ho, Yan
Friesen, Travis
Suh, Kwang S.
Yuspa, Stuart H.
TGF-β signalling is regulated by Schnurri-2 dependent nuclear translocation of CLIC4 and consequent stabilization of phospho Smad2–3
title TGF-β signalling is regulated by Schnurri-2 dependent nuclear translocation of CLIC4 and consequent stabilization of phospho Smad2–3
title_full TGF-β signalling is regulated by Schnurri-2 dependent nuclear translocation of CLIC4 and consequent stabilization of phospho Smad2–3
title_fullStr TGF-β signalling is regulated by Schnurri-2 dependent nuclear translocation of CLIC4 and consequent stabilization of phospho Smad2–3
title_full_unstemmed TGF-β signalling is regulated by Schnurri-2 dependent nuclear translocation of CLIC4 and consequent stabilization of phospho Smad2–3
title_short TGF-β signalling is regulated by Schnurri-2 dependent nuclear translocation of CLIC4 and consequent stabilization of phospho Smad2–3
title_sort tgf-β signalling is regulated by schnurri-2 dependent nuclear translocation of clic4 and consequent stabilization of phospho smad2–3
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825893/
https://www.ncbi.nlm.nih.gov/pubmed/19448624
http://dx.doi.org/10.1038/ncb1885
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