气候变化领域集成服务门户(CCPortal): Sulfated glycosaminoglycans mediate prion-like behavior of p53 aggregates

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DOI	10.1073/PNAS.2009931117
	Sulfated glycosaminoglycans mediate prion-like behavior of p53 aggregates
	Iwahashi N.; Ikezaki M.; Nishikawa T.; Namba N.; Ohgita T.; Saito H.; Ihara Y.; Shimanouchi T.; Ino K.; Uchimura K.; Nishitsuji K.
发表日期	2021
ISSN	00278424
起始页码	33225
结束页码	33234
卷号	117 期号:52
英文摘要	Sulfated glycosaminoglycans (GAGs) such as heparan sulfate (HS) are heteropolysaccharides implicated in the pathology of protein aggregation diseases including localized and systemic forms of amyloidosis. Among subdomains of sulfated GAGs, highly sulfated domains of HS, called HS S-domains, have been highlighted as being critical for HS function in amyloidoses. Recent studies suggest that the tumor suppressor p53 aggregates to form amyloid fibrils and propagates in a prion-like manner; however, molecules and mechanisms that are involved in the prion-like behavior of p53 aggregates have not been addressed. Here, we identified sulfated GAGs as molecules that mediate prion-like behavior of p53 aggregates. Sulfated GAGs at the cell surface were required for cellular uptake of recombinant and cancer cell-derived p53 aggregates and extracellular release of p53 from cancer cells. We further showed that HS S-domains accumulated within p53 deposits in human ovarian cancer tissues, and enzymatic remodeling of HS S-domains by Sulf-2 extracellular sulfatase down-regulated cellular uptake of p53 aggregates. Finally, sulfated GAG-dependent cellular uptake of p53 aggregates was critical for subsequent extracellular release of the aggregates and gain of oncogenic function in recipient cells. Our work provides a mechanism of prion-like behavior of p53 aggregates and will shed light on sulfated GAGs as a common mediator of prions. © 2020 National Academy of Sciences. All rights reserved.
英文关键词	Amyloid; Heparan sulfate; Ovarian cancer; P53; Protein aggregates
语种	英语
scopus关键词	glycosaminoglycan; heparan sulfate; protein aggregate; protein p53; recombinant protein; sulfate; animal; cell membrane; chemistry; CHO cell line; Cricetulus; endocytosis; female; genetics; human; metabolism; mutation; ovary tumor; pathology; prion; Animals; Cell Membrane; CHO Cells; Cricetulus; Endocytosis; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Mutation; Ovarian Neoplasms; Prions; Protein Aggregates; Recombinant Proteins; Sulfates; Tumor Suppressor Protein p53
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/179614
作者单位	Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama, 641-8509, Japan; Department of Biochemistry, Wakayama Medical University, Wakayama, 641-8509, Japan; Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Kyoto, 607-8414, Japan; Graduate School of Environmental and Life Science, Okayama University, Okayama, 700-8530, Japan; Unité de Glycobiologie Structurale et Fonctionnelle, UMR 8576 CNRS, Université de Lille, Villeneuve d’Ascq, 59655, France; Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, 770-8503, Japan
推荐引用方式 GB/T 7714	Iwahashi N.,Ikezaki M.,Nishikawa T.,et al. Sulfated glycosaminoglycans mediate prion-like behavior of p53 aggregates[J],2021,117(52).
APA	Iwahashi N..,Ikezaki M..,Nishikawa T..,Namba N..,Ohgita T..,...&Nishitsuji K..(2021).Sulfated glycosaminoglycans mediate prion-like behavior of p53 aggregates.Proceedings of the National Academy of Sciences of the United States of America,117(52).
MLA	Iwahashi N.,et al."Sulfated glycosaminoglycans mediate prion-like behavior of p53 aggregates".Proceedings of the National Academy of Sciences of the United States of America 117.52(2021).