Identification of two Wnt-responsive elements in the intron of RING finger protein 43 (RNF43) gene.

RING finger protein 43 (RNF43), an E3-type ubiquitin ligase, is frequently up-regulated in human colorectal cancer. It has been shown that expression of RNF43 is regulated by the Wnt-signaling pathway. However the regulatory region(s) for its transcriptional activation has not been clarified. In thi...

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Autores principales:	Norihiko Takahashi, Kiyoshi Yamaguchi, Tsuneo Ikenoue, Tomoaki Fujii, Yoichi Furukawa
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b690e06c1873474285a0753fa4c315aa
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spelling	oai:doaj.org-article:b690e06c1873474285a0753fa4c315aa2021-11-18T08:36:23ZIdentification of two Wnt-responsive elements in the intron of RING finger protein 43 (RNF43) gene.1932-620310.1371/journal.pone.0086582https://doaj.org/article/b690e06c1873474285a0753fa4c315aa2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24466159/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203RING finger protein 43 (RNF43), an E3-type ubiquitin ligase, is frequently up-regulated in human colorectal cancer. It has been shown that expression of RNF43 is regulated by the Wnt-signaling pathway. However the regulatory region(s) for its transcriptional activation has not been clarified. In this study, we have shown for the first time that RNF43 is a direct target of TCF4/β-catenin complex, and that its expression is regulated by a regulatory region containing two Wnt-responsive elements (WREs) in intron2. A reporter gene assay revealed that nucleotide substitutions in the WREs decreased the reporter activity in colon cancer cells, suggesting that both WREs are involved in the transcriptional activation. Knockdown of β-catenin by siRNA suppressed the reporter activity. In addition, ChIP assay showed that both elements associate with TCF4/β-catenin complex in colon cancer cells. These data indicate that expression of RNF43 is regulated by the canonical Wnt/β-catenin pathway through binding of the WREs with TCF4/β-catenin complex. These findings should be useful for the understanding of the regulatory mechanism of RNF43 and may contribute to the clarification of signaling pathways regulated by RNF43.Norihiko TakahashiKiyoshi YamaguchiTsuneo IkenoueTomoaki FujiiYoichi FurukawaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e86582 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Norihiko Takahashi Kiyoshi Yamaguchi Tsuneo Ikenoue Tomoaki Fujii Yoichi Furukawa Identification of two Wnt-responsive elements in the intron of RING finger protein 43 (RNF43) gene.
description	RING finger protein 43 (RNF43), an E3-type ubiquitin ligase, is frequently up-regulated in human colorectal cancer. It has been shown that expression of RNF43 is regulated by the Wnt-signaling pathway. However the regulatory region(s) for its transcriptional activation has not been clarified. In this study, we have shown for the first time that RNF43 is a direct target of TCF4/β-catenin complex, and that its expression is regulated by a regulatory region containing two Wnt-responsive elements (WREs) in intron2. A reporter gene assay revealed that nucleotide substitutions in the WREs decreased the reporter activity in colon cancer cells, suggesting that both WREs are involved in the transcriptional activation. Knockdown of β-catenin by siRNA suppressed the reporter activity. In addition, ChIP assay showed that both elements associate with TCF4/β-catenin complex in colon cancer cells. These data indicate that expression of RNF43 is regulated by the canonical Wnt/β-catenin pathway through binding of the WREs with TCF4/β-catenin complex. These findings should be useful for the understanding of the regulatory mechanism of RNF43 and may contribute to the clarification of signaling pathways regulated by RNF43.
format	article
author	Norihiko Takahashi Kiyoshi Yamaguchi Tsuneo Ikenoue Tomoaki Fujii Yoichi Furukawa
author_facet	Norihiko Takahashi Kiyoshi Yamaguchi Tsuneo Ikenoue Tomoaki Fujii Yoichi Furukawa
author_sort	Norihiko Takahashi
title	Identification of two Wnt-responsive elements in the intron of RING finger protein 43 (RNF43) gene.
title_short	Identification of two Wnt-responsive elements in the intron of RING finger protein 43 (RNF43) gene.
title_full	Identification of two Wnt-responsive elements in the intron of RING finger protein 43 (RNF43) gene.
title_fullStr	Identification of two Wnt-responsive elements in the intron of RING finger protein 43 (RNF43) gene.
title_full_unstemmed	Identification of two Wnt-responsive elements in the intron of RING finger protein 43 (RNF43) gene.
title_sort	identification of two wnt-responsive elements in the intron of ring finger protein 43 (rnf43) gene.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/b690e06c1873474285a0753fa4c315aa
work_keys_str_mv	AT norihikotakahashi identificationoftwowntresponsiveelementsintheintronofringfingerprotein43rnf43gene AT kiyoshiyamaguchi identificationoftwowntresponsiveelementsintheintronofringfingerprotein43rnf43gene AT tsuneoikenoue identificationoftwowntresponsiveelementsintheintronofringfingerprotein43rnf43gene AT tomoakifujii identificationoftwowntresponsiveelementsintheintronofringfingerprotein43rnf43gene AT yoichifurukawa identificationoftwowntresponsiveelementsintheintronofringfingerprotein43rnf43gene
_version_	1718421582557216768

Identification of two Wnt-responsive elements in the intron of RING finger protein 43 (RNF43) gene.

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