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WD-repeat protein WDR13 is a novel transcriptional regulator of c-Jun and modulates intestinal homeostasis in mice

BACKGROUND: WDR13 is a member of the WD repeat protein family and is expressed in several tissues of human and mice. Previous studies in our laboratory showed that the lack of this gene in mice resulted in mild obesity, hyperinsulinemia, enhanced beta cell proliferation and protection from inflammat...

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Autores principales: Singh, Vijay Pratap, Katta, Saritha, Kumar, Satish
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320654/
https://www.ncbi.nlm.nih.gov/pubmed/28222755
http://dx.doi.org/10.1186/s12885-017-3118-7
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author Singh, Vijay Pratap
Katta, Saritha
Kumar, Satish
author_facet Singh, Vijay Pratap
Katta, Saritha
Kumar, Satish
author_sort Singh, Vijay Pratap
collection PubMed
description BACKGROUND: WDR13 is a member of the WD repeat protein family and is expressed in several tissues of human and mice. Previous studies in our laboratory showed that the lack of this gene in mice resulted in mild obesity, hyperinsulinemia, enhanced beta cell proliferation and protection from inflammation. However, the molecular mechanism of WDR13 action is not well understood. METHODS: In the present study, we used AOM/DSS to induce colitis-mediated colorectal tumor after establishing expression of Wdr13 gene in colon. Further, we have used human colon cancer cell lines, HT29 and COLO205, and mouse primary embryonic fibroblast to understand the molecular mechanism of WDR13 action. RESULTS: We observed that mice lacking Wdr13 gene have reduced number of tumors and are more susceptible to DSS-induced colon ulcers. We also show that WDR13 is a part of multi protein complex c-Jun/NCoR1/HDAC3 and it acts as a transcriptional activator of AP1 target genes in the presence of JNK signal. Consistent with in vitro data, we observed reduced expression of AP1 target genes in colon after AOM/DSS treatment in Wdr13 knockout mice as compared to that in wild type. CONCLUSION: Mice lacking Wdr13 gene showed reduced expression of AP1 target genes and protection from colitis-induced colorectal tumors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-017-3118-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-53206542017-02-24 WD-repeat protein WDR13 is a novel transcriptional regulator of c-Jun and modulates intestinal homeostasis in mice Singh, Vijay Pratap Katta, Saritha Kumar, Satish BMC Cancer Research Article BACKGROUND: WDR13 is a member of the WD repeat protein family and is expressed in several tissues of human and mice. Previous studies in our laboratory showed that the lack of this gene in mice resulted in mild obesity, hyperinsulinemia, enhanced beta cell proliferation and protection from inflammation. However, the molecular mechanism of WDR13 action is not well understood. METHODS: In the present study, we used AOM/DSS to induce colitis-mediated colorectal tumor after establishing expression of Wdr13 gene in colon. Further, we have used human colon cancer cell lines, HT29 and COLO205, and mouse primary embryonic fibroblast to understand the molecular mechanism of WDR13 action. RESULTS: We observed that mice lacking Wdr13 gene have reduced number of tumors and are more susceptible to DSS-induced colon ulcers. We also show that WDR13 is a part of multi protein complex c-Jun/NCoR1/HDAC3 and it acts as a transcriptional activator of AP1 target genes in the presence of JNK signal. Consistent with in vitro data, we observed reduced expression of AP1 target genes in colon after AOM/DSS treatment in Wdr13 knockout mice as compared to that in wild type. CONCLUSION: Mice lacking Wdr13 gene showed reduced expression of AP1 target genes and protection from colitis-induced colorectal tumors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-017-3118-7) contains supplementary material, which is available to authorized users. BioMed Central 2017-02-21 /pmc/articles/PMC5320654/ /pubmed/28222755 http://dx.doi.org/10.1186/s12885-017-3118-7 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Singh, Vijay Pratap
Katta, Saritha
Kumar, Satish
WD-repeat protein WDR13 is a novel transcriptional regulator of c-Jun and modulates intestinal homeostasis in mice
title WD-repeat protein WDR13 is a novel transcriptional regulator of c-Jun and modulates intestinal homeostasis in mice
title_full WD-repeat protein WDR13 is a novel transcriptional regulator of c-Jun and modulates intestinal homeostasis in mice
title_fullStr WD-repeat protein WDR13 is a novel transcriptional regulator of c-Jun and modulates intestinal homeostasis in mice
title_full_unstemmed WD-repeat protein WDR13 is a novel transcriptional regulator of c-Jun and modulates intestinal homeostasis in mice
title_short WD-repeat protein WDR13 is a novel transcriptional regulator of c-Jun and modulates intestinal homeostasis in mice
title_sort wd-repeat protein wdr13 is a novel transcriptional regulator of c-jun and modulates intestinal homeostasis in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320654/
https://www.ncbi.nlm.nih.gov/pubmed/28222755
http://dx.doi.org/10.1186/s12885-017-3118-7
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