气候变化领域集成服务门户(CCPortal): A role for keratin 17 during DNA damage response and tumor initiation

CCPortal

DOI	10.1073/PNAS.2020150118
	A role for keratin 17 during DNA damage response and tumor initiation
	Nair R.R.; Hsu J.; Jacob J.T.; Pineda C.M.; Hobbs R.P.; Coulombe P.A.
发表日期	2021
ISSN	00278424
卷号	118 期号:13
英文摘要	High levels of the intermediate filament protein keratin 17 (K17) are associated with poor prognoses for several human carcinomas. Studies in mouse models have shown that K17 expression is positively associated with growth, survival, and inflammation in skin and that lack of K17 delays onset of tumorigenesis. K17 occurs in the nucleus of human and mouse tumor keratinocytes where it impacts chromatin architecture, gene expression, and cell proliferation. We report here that K17 is induced following DNA damage and promotes keratinocyte survival. The presence of nuclear K17 is required at an early stage of the double-stranded break (DSB) arm of the DNA damage and repair (DDR) cascade, consistent with its ability to associate with key DDR effectors, including γ-H2A.X, 53BP1, and DNA-PKcs. Mice lacking K17 or with attenuated K17 nuclear import showed curtailed initiation in a two-step skin carcinogenesis paradigm. The impact of nuclear-localized K17 on DDR and cell survival provides a basis for the link between K17 induction and poor clinical outcomes for several human carcinomas. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	DNA damage; Intermediate filament; Keratin; Skin; Tumor
语种	英语
scopus关键词	cytokeratin 17; DNA; double stranded DNA; histone H2AX; protein kinase; tumor suppressor p53 binding protein 1; animal cell; animal experiment; animal model; Article; cancer prognosis; cancer survival; cell nucleus; cell proliferation; cell survival; chromatin; controlled study; disease association; DNA damage; DNA damage response; DNA repair; DNA strand breakage; female; gene expression; HeLa cell line; human; human cell; inflammation; keratinocyte; male; mouse; mouse model; newborn; nonhuman; nuclear import; priority journal; protein expression; protein induction; protein localization; skin cancer; skin carcinogenesis; tumor growth
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180054
作者单位	Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, United States; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, United States; Department of Dermatology, University of Michigan, Ann Arbor, MI 48109, United States; Rogel Cancer Center, University of Michigan, Ann Arbor, MI 48109, United States; Department of Dermatology, Penn State College of Medicine, Hershey, PA 17033, United States
推荐引用方式 GB/T 7714	Nair R.R.,Hsu J.,Jacob J.T.,et al. A role for keratin 17 during DNA damage response and tumor initiation[J],2021,118(13).
APA	Nair R.R.,Hsu J.,Jacob J.T.,Pineda C.M.,Hobbs R.P.,&Coulombe P.A..(2021).A role for keratin 17 during DNA damage response and tumor initiation.Proceedings of the National Academy of Sciences of the United States of America,118(13).
MLA	Nair R.R.,et al."A role for keratin 17 during DNA damage response and tumor initiation".Proceedings of the National Academy of Sciences of the United States of America 118.13(2021).