Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism

Abstract TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is...

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Autores principales:	Wenjuan Liao, Hongbing Liu, Yiwei Zhang, Ji Hoon Jung, Jiaxiang Chen, Xiaohua Su, Yeong C. Kim, Elsa R Flores, San Ming Wang, Malwina Czarny-Ratajczak, Wen Li, Shelya X. Zeng, Hua Lu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2e372028561d4dfc9c57e1043564aa0b
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spelling	oai:doaj.org-article:2e372028561d4dfc9c57e1043564aa0b2021-12-02T12:32:29ZCcdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism10.1038/s41598-017-09228-82045-2322https://doaj.org/article/2e372028561d4dfc9c57e1043564aa0b2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09228-8https://doaj.org/toc/2045-2322Abstract TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63. Also, the expression of CCDC3 is positively correlated with TAp63 levels, but conversely with ΔNp63 levels, during adipocyte differentiation. Interestingly, CCDC3, as a secreted protein, targets liver cancer cells and increases long chain polyunsaturated fatty acids, but decreases ceramide in the cells. CCDC3 alleviates glucose intolerance, insulin resistance and steatosis formation in transgenic CCDC3 mice on high-fat diet (HFD) by reducing the expression of hepatic PPARγ and its target gene CIDEA as well as other genes involved in de novo lipogenesis. Similar results are reproduced by hepatic expression of ectopic CCDC3 in mice on HFD. Altogether, these results demonstrate that CCDC3 modulates liver lipid metabolism by inhibiting liver de novo lipogenesis as a downstream player of the p63 network.Wenjuan LiaoHongbing LiuYiwei ZhangJi Hoon JungJiaxiang ChenXiaohua SuYeong C. KimElsa R FloresSan Ming WangMalwina Czarny-RatajczakWen LiShelya X. ZengHua LuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wenjuan Liao Hongbing Liu Yiwei Zhang Ji Hoon Jung Jiaxiang Chen Xiaohua Su Yeong C. Kim Elsa R Flores San Ming Wang Malwina Czarny-Ratajczak Wen Li Shelya X. Zeng Hua Lu Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism
description	Abstract TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63. Also, the expression of CCDC3 is positively correlated with TAp63 levels, but conversely with ΔNp63 levels, during adipocyte differentiation. Interestingly, CCDC3, as a secreted protein, targets liver cancer cells and increases long chain polyunsaturated fatty acids, but decreases ceramide in the cells. CCDC3 alleviates glucose intolerance, insulin resistance and steatosis formation in transgenic CCDC3 mice on high-fat diet (HFD) by reducing the expression of hepatic PPARγ and its target gene CIDEA as well as other genes involved in de novo lipogenesis. Similar results are reproduced by hepatic expression of ectopic CCDC3 in mice on HFD. Altogether, these results demonstrate that CCDC3 modulates liver lipid metabolism by inhibiting liver de novo lipogenesis as a downstream player of the p63 network.
format	article
author	Wenjuan Liao Hongbing Liu Yiwei Zhang Ji Hoon Jung Jiaxiang Chen Xiaohua Su Yeong C. Kim Elsa R Flores San Ming Wang Malwina Czarny-Ratajczak Wen Li Shelya X. Zeng Hua Lu
author_facet	Wenjuan Liao Hongbing Liu Yiwei Zhang Ji Hoon Jung Jiaxiang Chen Xiaohua Su Yeong C. Kim Elsa R Flores San Ming Wang Malwina Czarny-Ratajczak Wen Li Shelya X. Zeng Hua Lu
author_sort	Wenjuan Liao
title	Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism
title_short	Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism
title_full	Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism
title_fullStr	Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism
title_full_unstemmed	Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism
title_sort	ccdc3: a new p63 target involved in regulation of liver lipid metabolism
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2e372028561d4dfc9c57e1043564aa0b
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Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism

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