IKKα mediates UVB-induced cell apoptosis by regulating p53 pathway activation

Exposure to ultraviolet B (UVB) has been demonstrated to induce DNA damage as well as angiogenesis-related photo-damages, which are implicated in a variety of medical problems, including sunburn, photo-aging and skin cancers. However, the molecular mechanism related to UVB-induced photo-injuries rem...

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Autores principales:	Hongli Wang, Min Zhang, Xiuduan Xu, Shaojun Hou, Zhihui Liu, Xuejiao Chen, Chongchong Zhang, Huan Xu, Lin Wu, Kun Liu, Lun Song
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	IKKα P53 UVB Apoptosis PERP Environmental pollution TD172-193.5 Environmental sciences GE1-350
Acceso en línea:	https://doaj.org/article/2e47407df2da434e9f7f672e45cf7257
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spelling	oai:doaj.org-article:2e47407df2da434e9f7f672e45cf72572021-11-06T04:15:17ZIKKα mediates UVB-induced cell apoptosis by regulating p53 pathway activation0147-651310.1016/j.ecoenv.2021.112892https://doaj.org/article/2e47407df2da434e9f7f672e45cf72572021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0147651321010046https://doaj.org/toc/0147-6513Exposure to ultraviolet B (UVB) has been demonstrated to induce DNA damage as well as angiogenesis-related photo-damages, which are implicated in a variety of medical problems, including sunburn, photo-aging and skin cancers. However, the molecular mechanism related to UVB-induced photo-injuries remained fully elucidated. Here we revealed that one of the catalytic subunits of the IKK complex, IKKα, played a critical role in mediating UVB-induced apoptotic responses in two kinds of UVB sensitive cells, human keratinocyte (HaCat) and mouse embryonic fibroblasts (MEFs). This function of IKKα was unrelated to NF-κB activity, but was delivered by inducing phosphorylation and acetylation of p53 and upregulating the expression of the pro-apoptotic p53 target gene, PERP. Although IKKα kinase activity was required for mediating post-translational modifications and transactivation of 53 and PERP induction, IKKα did not show direct binding ability toward p53. Instead, IKKα could interact with CHK1, the protein kinase leading to p53 phosphorylation, and trigger CHK1 activation and CHK1/p53 complex formation. At the same time, IKKα could also interact with p300 and CBP, the acetyltransferases responsible for p53 acetylation, and trigger p300/CBP activation and p300/p53 or CBP/p53 complex formation under UVB exposure. Taken together, we have identified a novel NF-κB-independent role of IKKα in mediating UVB-induced apoptosis by regulating p53 pathway activation. Targeting IKKα/p53/PERP pathway might be helpful to prevent skin photo-damages induced by sunlight.Hongli WangMin ZhangXiuduan XuShaojun HouZhihui LiuXuejiao ChenChongchong ZhangHuan XuLin WuKun LiuLun SongElsevierarticleIKKαP53UVBApoptosisPERPEnvironmental pollutionTD172-193.5Environmental sciencesGE1-350ENEcotoxicology and Environmental Safety, Vol 227, Iss , Pp 112892- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	IKKα P53 UVB Apoptosis PERP Environmental pollution TD172-193.5 Environmental sciences GE1-350
spellingShingle	IKKα P53 UVB Apoptosis PERP Environmental pollution TD172-193.5 Environmental sciences GE1-350 Hongli Wang Min Zhang Xiuduan Xu Shaojun Hou Zhihui Liu Xuejiao Chen Chongchong Zhang Huan Xu Lin Wu Kun Liu Lun Song IKKα mediates UVB-induced cell apoptosis by regulating p53 pathway activation
description	Exposure to ultraviolet B (UVB) has been demonstrated to induce DNA damage as well as angiogenesis-related photo-damages, which are implicated in a variety of medical problems, including sunburn, photo-aging and skin cancers. However, the molecular mechanism related to UVB-induced photo-injuries remained fully elucidated. Here we revealed that one of the catalytic subunits of the IKK complex, IKKα, played a critical role in mediating UVB-induced apoptotic responses in two kinds of UVB sensitive cells, human keratinocyte (HaCat) and mouse embryonic fibroblasts (MEFs). This function of IKKα was unrelated to NF-κB activity, but was delivered by inducing phosphorylation and acetylation of p53 and upregulating the expression of the pro-apoptotic p53 target gene, PERP. Although IKKα kinase activity was required for mediating post-translational modifications and transactivation of 53 and PERP induction, IKKα did not show direct binding ability toward p53. Instead, IKKα could interact with CHK1, the protein kinase leading to p53 phosphorylation, and trigger CHK1 activation and CHK1/p53 complex formation. At the same time, IKKα could also interact with p300 and CBP, the acetyltransferases responsible for p53 acetylation, and trigger p300/CBP activation and p300/p53 or CBP/p53 complex formation under UVB exposure. Taken together, we have identified a novel NF-κB-independent role of IKKα in mediating UVB-induced apoptosis by regulating p53 pathway activation. Targeting IKKα/p53/PERP pathway might be helpful to prevent skin photo-damages induced by sunlight.
format	article
author	Hongli Wang Min Zhang Xiuduan Xu Shaojun Hou Zhihui Liu Xuejiao Chen Chongchong Zhang Huan Xu Lin Wu Kun Liu Lun Song
author_facet	Hongli Wang Min Zhang Xiuduan Xu Shaojun Hou Zhihui Liu Xuejiao Chen Chongchong Zhang Huan Xu Lin Wu Kun Liu Lun Song
author_sort	Hongli Wang
title	IKKα mediates UVB-induced cell apoptosis by regulating p53 pathway activation
title_short	IKKα mediates UVB-induced cell apoptosis by regulating p53 pathway activation
title_full	IKKα mediates UVB-induced cell apoptosis by regulating p53 pathway activation
title_fullStr	IKKα mediates UVB-induced cell apoptosis by regulating p53 pathway activation
title_full_unstemmed	IKKα mediates UVB-induced cell apoptosis by regulating p53 pathway activation
title_sort	ikkα mediates uvb-induced cell apoptosis by regulating p53 pathway activation
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/2e47407df2da434e9f7f672e45cf7257
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_version_	1718443907148152832

IKKα mediates UVB-induced cell apoptosis by regulating p53 pathway activation

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