Forward Genetic Screening for Regulators Involved in Cholesterol Synthesis Using Validation-Based Insertional Mutagenesis
文献类型:期刊论文
作者 | Jiang, W; Tang, JJ; Miao, HH; Qu, YX; Qin, J; Xu, J; Yang, JB; Li, BL; Song, BL |
刊名 | PLOS ONE
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出版日期 | 2014 |
卷号 | 9期号:11页码:e112632-e112632 |
通讯作者 | Yang, JB (reprint author), Lanzhou Univ, Sch Life Sci, Lanzhou 730000, Peoples R China.,yangjb@lzu.edu.cn ; blsong@whu.edu.cn |
英文摘要 | Somatic cell genetics is a powerful approach for unraveling the regulatory mechanism of cholesterol metabolism. However, it is difficult to identify the mutant gene(s) due to cells are usually mutagenized chemically or physically. To identify important genes controlling cholesterol biosynthesis, an unbiased forward genetics approach named validation-based insertional mutagenesis (VBIM) system was used to isolate and characterize the 25-hydroxycholesterol (25-HC)-resistant and SR-12813-resisitant mutants. Here we report that five mutant cell lines were isolated. Among which, four sterol-resistant mutants either contain a truncated NH2-terminal domain of sterol regulatory element-binding protein (SREBP)-2 terminating at amino acids (aa) 400, or harbor an overexpressed SREBP cleavage-activating protein (SCAP). Besides, one SR-12813 resistant mutant was identified to contain a truncated COOH-terminal catalytic domain of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMG-CoA reductase). This study demonstrates that the VBIM system can be a powerful tool to screen novel regulatory genes in cholesterol biosynthesis. |
学科主题 | Science & Technology - Other Topics |
类目[WOS] | Multidisciplinary Sciences |
关键词[WOS] | HMG-COA REDUCTASE ; HAMSTER OVARY CELLS ; ENDOPLASMIC-RETICULUM ; FEEDBACK-REGULATION ; STEROL RESISTANCE ; DEGRADATION ; INSIG-1 ; UBIQUITINATION ; PROTEIN ; BINDING |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000349145400021 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/240] ![]() |
专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
推荐引用方式 GB/T 7714 | Jiang, W,Tang, JJ,Miao, HH,et al. Forward Genetic Screening for Regulators Involved in Cholesterol Synthesis Using Validation-Based Insertional Mutagenesis[J]. PLOS ONE,2014,9(11):e112632-e112632. |
APA | Jiang, W.,Tang, JJ.,Miao, HH.,Qu, YX.,Qin, J.,...&Song, BL.(2014).Forward Genetic Screening for Regulators Involved in Cholesterol Synthesis Using Validation-Based Insertional Mutagenesis.PLOS ONE,9(11),e112632-e112632. |
MLA | Jiang, W,et al."Forward Genetic Screening for Regulators Involved in Cholesterol Synthesis Using Validation-Based Insertional Mutagenesis".PLOS ONE 9.11(2014):e112632-e112632. |
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