Nuclear accumulation of symplekin promotes cellular proliferation and dedifferentiation in an ERK1/2-dependent manner

Abstract Symplekin is a multifunctional protein that localizes to both tight junctions and the nucleus in polarized epithelial cells, with confirmed roles in mRNA maturation, transcriptional modulation and tight-junction assembly. However, the mechanisms governing its subcellular distribution and re...

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Autores principales:	Chen Zhang, Hai-Lei Mao, Yi Cao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3f4498b4bac44c33a7929baa51c7da9f
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spelling	oai:doaj.org-article:3f4498b4bac44c33a7929baa51c7da9f2021-12-02T15:05:56ZNuclear accumulation of symplekin promotes cellular proliferation and dedifferentiation in an ERK1/2-dependent manner10.1038/s41598-017-04005-z2045-2322https://doaj.org/article/3f4498b4bac44c33a7929baa51c7da9f2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04005-zhttps://doaj.org/toc/2045-2322Abstract Symplekin is a multifunctional protein that localizes to both tight junctions and the nucleus in polarized epithelial cells, with confirmed roles in mRNA maturation, transcriptional modulation and tight-junction assembly. However, the mechanisms governing its subcellular distribution and related functions remain unclear. In this study, we found that symplekin primarily localizes to the nuclei of cultured dedifferentiated colorectal cancer cells, and nuclear symplekin showed higher phosphorylation and binding affinity with YBX3 than its membrane fraction. Moreover, the accumulation of nuclear symplekin promoted cell proliferation and dedifferentiation as well as β-catenin transactivation in vitro. Nuclear symplekin acts as a transcriptional co-activator for the expression of many cell cycle-related genes. Furthermore, extracellular signal-regulated kinase (ERK) phosphorylated symplekin at T1257 to facilitate its nuclear accumulation upon epidermal growth factor (EGF) stimulation. Meanwhile, reduction of total symplekin also induced certain epithelial-mesenchymal transition features in HT-29 cells. Taken together, our results confirm the coordinated roles of symplekin in cell junctions and gene transcription, which are related to its subcellular localization. The significance of nuclear symplekin in tumorigenesis is also highlighted, and ERK-dependent phosphorylation represents a mechanism for its subcellular sorting.Chen ZhangHai-Lei MaoYi CaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chen Zhang Hai-Lei Mao Yi Cao Nuclear accumulation of symplekin promotes cellular proliferation and dedifferentiation in an ERK1/2-dependent manner
description	Abstract Symplekin is a multifunctional protein that localizes to both tight junctions and the nucleus in polarized epithelial cells, with confirmed roles in mRNA maturation, transcriptional modulation and tight-junction assembly. However, the mechanisms governing its subcellular distribution and related functions remain unclear. In this study, we found that symplekin primarily localizes to the nuclei of cultured dedifferentiated colorectal cancer cells, and nuclear symplekin showed higher phosphorylation and binding affinity with YBX3 than its membrane fraction. Moreover, the accumulation of nuclear symplekin promoted cell proliferation and dedifferentiation as well as β-catenin transactivation in vitro. Nuclear symplekin acts as a transcriptional co-activator for the expression of many cell cycle-related genes. Furthermore, extracellular signal-regulated kinase (ERK) phosphorylated symplekin at T1257 to facilitate its nuclear accumulation upon epidermal growth factor (EGF) stimulation. Meanwhile, reduction of total symplekin also induced certain epithelial-mesenchymal transition features in HT-29 cells. Taken together, our results confirm the coordinated roles of symplekin in cell junctions and gene transcription, which are related to its subcellular localization. The significance of nuclear symplekin in tumorigenesis is also highlighted, and ERK-dependent phosphorylation represents a mechanism for its subcellular sorting.
format	article
author	Chen Zhang Hai-Lei Mao Yi Cao
author_facet	Chen Zhang Hai-Lei Mao Yi Cao
author_sort	Chen Zhang
title	Nuclear accumulation of symplekin promotes cellular proliferation and dedifferentiation in an ERK1/2-dependent manner
title_short	Nuclear accumulation of symplekin promotes cellular proliferation and dedifferentiation in an ERK1/2-dependent manner
title_full	Nuclear accumulation of symplekin promotes cellular proliferation and dedifferentiation in an ERK1/2-dependent manner
title_fullStr	Nuclear accumulation of symplekin promotes cellular proliferation and dedifferentiation in an ERK1/2-dependent manner
title_full_unstemmed	Nuclear accumulation of symplekin promotes cellular proliferation and dedifferentiation in an ERK1/2-dependent manner
title_sort	nuclear accumulation of symplekin promotes cellular proliferation and dedifferentiation in an erk1/2-dependent manner
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3f4498b4bac44c33a7929baa51c7da9f
work_keys_str_mv	AT chenzhang nuclearaccumulationofsymplekinpromotescellularproliferationanddedifferentiationinanerk12dependentmanner AT haileimao nuclearaccumulationofsymplekinpromotescellularproliferationanddedifferentiationinanerk12dependentmanner AT yicao nuclearaccumulationofsymplekinpromotescellularproliferationanddedifferentiationinanerk12dependentmanner
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Nuclear accumulation of symplekin promotes cellular proliferation and dedifferentiation in an ERK1/2-dependent manner

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