Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2 through competitive oxidation
文献类型：期刊论文
| 作者 | Wang, Yong-Jian3,4; Bian, Yan3; Lu, Ming3; Xiong, Ying3; Li, Qin3; Li, Bo-Liang3; Luo, Jie1; Song, Bao-Liang1; Guo, Shu-Yuan5; Yin, Hui-Yong5 |
| 刊名 | NATURE CELL BIOLOGY
 |
| 出版日期 | 2017 |
| 卷号 | 19期号:7页码:808-+ |
| 关键词 | circadian rhythms BMAL1 macaque monkey sleep disruption psychosis aging |
| ISSN号 | 1465-7392 |
| DOI | 10.1038/ncb3551 |
| 文献子类 | Article |
| 英文摘要 | Ubiquitin linkage to cysteine is an unconventional modification targeting protein for degradation. However, the physiological regulation of cysteine ubiquitylation is still mysterious. Here we found that ACAT2, a cellular enzyme converting cholesterol and fatty acid to cholesteryl esters, was ubiquitylated on Cys277 for degradation when the lipid level was low. gp78-Insigs catalysed Lys48-linked polyubiquitylation on this Cys277. A high concentration of cholesterol and fatty acid, however, induced cellular reactive oxygen species (ROS) that oxidized Cys277, resulting in ACAT2 stabilization and subsequently elevated cholesteryl esters. Furthermore, ACAT2 knockout mice were more susceptible to high-fat diet-associated insulin resistance. By contrast, expression of a constitutively stable form of ACAT2 (C277A) resulted in higher insulin sensitivity. Together, these data indicate that lipid-induced stabilization of ACAT2 ameliorates lipotoxicity from excessive cholesterol and fatty acid. This unconventional cysteine ubiquitylation of ACAT2 constitutes an important mechanism for sensing lipid-overload-induced ROS and fine-tuning lipid homeostasis. |
| 学科主题 | Cell Biology |
| WOS关键词 | HMG-COA REDUCTASE ; RETICULUM-ASSOCIATED DEGRADATION ; MOTILITY FACTOR-RECEPTOR ; ENDOPLASMIC-RETICULUM ; UBIQUITIN LIGASE ; ACYL-COENZYME ; GENETIC ARCHITECTURE ; INSULIN-RESISTANCE ; CHEMICAL PROBES ; IN-VITRO |
| 语种 | 英语 |
| WOS记录号 | WOS:000404408800013 |
| 出版者 | NATURE PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/631]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Wuhan Univ, Inst Adv Studies, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Peoples R China; 2.Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA, 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China; 4.Jiangsu Normal Univ, Sch Life Sci, Key Lab Biotechnol Med Plants Jiangsu Prov, Xuzhou 221116, Jiangsu, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab food safety Res, Shanghai 200031, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wang, Yong-Jian,Bian, Yan,Lu, Ming,et al. Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2 through competitive oxidation[J]. NATURE CELL BIOLOGY,2017,19(7):808-+. |
| APA | Wang, Yong-Jian.,Bian, Yan.,Lu, Ming.,Xiong, Ying.,Li, Qin.,...&,.(2017).Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2 through competitive oxidation.NATURE CELL BIOLOGY,19(7),808-+. |
| MLA | Wang, Yong-Jian,et al."Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2 through competitive oxidation".NATURE CELL BIOLOGY 19.7(2017):808-+. |
入库方式： OAI收割
来源：上海营养与健康研究所
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