Transcriptional regulation of the tumor suppressor FHL2 by p53 in human kidney and liver cells.

Four and a Half LIM protein 2 (FHL2) is a LIM domain only protein that is able to form various protein complexes and regulate gene transcription. Recent findings showed that FHL2 is a potential tumor suppressor gene that was down-regulated in hepatocellular carcinoma (HCC). Moreover, FHL2 can bind t...

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Autores principales:	Jiaying Xu, Junwei Zhou, Man-Shan Li, Chor-Fung Ng, Yuen-Keng Ng, Paul Bo-San Lai, Stephen Kwok-Wing Tsui
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7e9810a733054538a1e0067e8eec9c4a
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spelling	oai:doaj.org-article:7e9810a733054538a1e0067e8eec9c4a2021-11-25T06:04:48ZTranscriptional regulation of the tumor suppressor FHL2 by p53 in human kidney and liver cells.1932-620310.1371/journal.pone.0099359https://doaj.org/article/7e9810a733054538a1e0067e8eec9c4a2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25121502/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Four and a Half LIM protein 2 (FHL2) is a LIM domain only protein that is able to form various protein complexes and regulate gene transcription. Recent findings showed that FHL2 is a potential tumor suppressor gene that was down-regulated in hepatocellular carcinoma (HCC). Moreover, FHL2 can bind to and activate the TP53 promoter in hepatic cells. In this study, the activity of the two promoters of FHL2, 1a and 1b, were determined in the human embryonic kidney cell line HEK293 and the activation of these two promoters by p53 was investigated. Our results showed that the 1b promoter has a higher activity than the 1a promoter in HEK 293 cells but the 1a promoter is more responsive to the activation by p53 when compared with the 1b promoter. The regulation of FHL2 by p53 was further confirmed in liver cells by the overexpression of p53 in Hep3B cells and the knockdown of p53 in HepG2 cells. Combining promoter activity results of truncated mutants and predictions by bioinformatics tools, a putative p53 binding site was found in the exon 1a of FHL2 from +213 to +232. The binding between the p53 protein and the putative p53 binding site was then validated by the ChIP assay. Furthermore, the expression of FHL2 and TP53 were down-regulated in majority of HCC tumour samples (n = 41) and significantly correlated (P = 0.026). Finally, we found that the somatic mutation 747 (G→T), a hot spot mutation of the TP53 gene, is potentially associated with a higher expression of FHL2 in HCC tumour samples. Taken together, this is the first in-depth study about the transcriptional regulation of FHL2 by p53.Jiaying XuJunwei ZhouMan-Shan LiChor-Fung NgYuen-Keng NgPaul Bo-San LaiStephen Kwok-Wing TsuiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e99359 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jiaying Xu Junwei Zhou Man-Shan Li Chor-Fung Ng Yuen-Keng Ng Paul Bo-San Lai Stephen Kwok-Wing Tsui Transcriptional regulation of the tumor suppressor FHL2 by p53 in human kidney and liver cells.
description	Four and a Half LIM protein 2 (FHL2) is a LIM domain only protein that is able to form various protein complexes and regulate gene transcription. Recent findings showed that FHL2 is a potential tumor suppressor gene that was down-regulated in hepatocellular carcinoma (HCC). Moreover, FHL2 can bind to and activate the TP53 promoter in hepatic cells. In this study, the activity of the two promoters of FHL2, 1a and 1b, were determined in the human embryonic kidney cell line HEK293 and the activation of these two promoters by p53 was investigated. Our results showed that the 1b promoter has a higher activity than the 1a promoter in HEK 293 cells but the 1a promoter is more responsive to the activation by p53 when compared with the 1b promoter. The regulation of FHL2 by p53 was further confirmed in liver cells by the overexpression of p53 in Hep3B cells and the knockdown of p53 in HepG2 cells. Combining promoter activity results of truncated mutants and predictions by bioinformatics tools, a putative p53 binding site was found in the exon 1a of FHL2 from +213 to +232. The binding between the p53 protein and the putative p53 binding site was then validated by the ChIP assay. Furthermore, the expression of FHL2 and TP53 were down-regulated in majority of HCC tumour samples (n = 41) and significantly correlated (P = 0.026). Finally, we found that the somatic mutation 747 (G→T), a hot spot mutation of the TP53 gene, is potentially associated with a higher expression of FHL2 in HCC tumour samples. Taken together, this is the first in-depth study about the transcriptional regulation of FHL2 by p53.
format	article
author	Jiaying Xu Junwei Zhou Man-Shan Li Chor-Fung Ng Yuen-Keng Ng Paul Bo-San Lai Stephen Kwok-Wing Tsui
author_facet	Jiaying Xu Junwei Zhou Man-Shan Li Chor-Fung Ng Yuen-Keng Ng Paul Bo-San Lai Stephen Kwok-Wing Tsui
author_sort	Jiaying Xu
title	Transcriptional regulation of the tumor suppressor FHL2 by p53 in human kidney and liver cells.
title_short	Transcriptional regulation of the tumor suppressor FHL2 by p53 in human kidney and liver cells.
title_full	Transcriptional regulation of the tumor suppressor FHL2 by p53 in human kidney and liver cells.
title_fullStr	Transcriptional regulation of the tumor suppressor FHL2 by p53 in human kidney and liver cells.
title_full_unstemmed	Transcriptional regulation of the tumor suppressor FHL2 by p53 in human kidney and liver cells.
title_sort	transcriptional regulation of the tumor suppressor fhl2 by p53 in human kidney and liver cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/7e9810a733054538a1e0067e8eec9c4a
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Transcriptional regulation of the tumor suppressor FHL2 by p53 in human kidney and liver cells.

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