Tetra-glutamic acid residues adjacent to Lys248 in HMG-CoA reductase are critical for the ubiquitination mediated by gp78 and UBE2G2 | |
Miao, HH; Jiang, W; Ge, LA; Li, BL; Song, BL | |
刊名 | ACTA BIOCHIMICA ET BIOPHYSICA SINICA |
2010 | |
卷号 | 42期号:5页码:303-310 |
关键词 | HMG-CoA reductase endoplasmic reticulum associated protein degradation (ERAD) tetraglutamic acid residue gp78 UBE2G2 |
通讯作者 | Song, BL (reprint author), Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.,blsong@sibs.ac.cn |
英文摘要 | Sterol-regulated degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) is a rapid feedback regulatory mechanism by which cells employ to control the cholesterol biosynthesis. This process is initiated by the sterol-induced interaction between HMGCR and Insig-1/gp78, a membrane-bound ubiquitin ligase complex. There are two Lys residues (Lys89 and Lys248) facing cytosol in the membrane domain of HMGCR, and Lys248 is the major ubiquitination site. In this study, we investigated the mechanism of ubiquitination site selection in HMGCR. We find that the distance of Lys248 to membrane is dispensable for its ubiquitination. However, the conserved tetra-glutamic acid residues adjacent to Lys248 in HMGCR are essential. Replacement of these negatively charged residues with tetra-arginine causes the resistance of HMGCR to sterol-induced ubiquitination and degradation, albeit this mutant HMGCR can still binds to Insig-1. We further find that the tetra-glutamic acid residues are necessary but not sufficient for the modification on their adjacent Lys, since they are not functional on Lys89 of HMGCR or in SCAP. UBE2G2, a previously known E2 of gp78, is demonstrated to be involved in the sterol-regulated ubiquitination and degradation of HMGCR. In summary, these results identify the tetra-glutamic acid residues as a critical motif in HMGCR for the ubiquitination reaction mediated by gp78 and UBE2G2. |
学科主题 | Biochemistry & Molecular Biology; Biophysics |
类目[WOS] | Biochemistry & Molecular Biology ; Biophysics |
关键词[WOS] | ELEMENT-BINDING PROTEINS ; CLEAVAGE-ACTIVATING PROTEIN ; COENZYME-A REDUCTASE ; ENDOPLASMIC-RETICULUM ; 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE ; DEGRADATION ; CHOLESTEROL ; INSIG-1 ; PATHWAY ; SREBPS |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000278421900001 |
内容类型 | 期刊论文 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/1004] |
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 | Miao, HH,Jiang, W,Ge, LA,et al. Tetra-glutamic acid residues adjacent to Lys248 in HMG-CoA reductase are critical for the ubiquitination mediated by gp78 and UBE2G2[J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA,2010,42(5):303-310. |
APA | Miao, HH,Jiang, W,Ge, LA,Li, BL,&Song, BL.(2010).Tetra-glutamic acid residues adjacent to Lys248 in HMG-CoA reductase are critical for the ubiquitination mediated by gp78 and UBE2G2.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,42(5),303-310. |
MLA | Miao, HH,et al."Tetra-glutamic acid residues adjacent to Lys248 in HMG-CoA reductase are critical for the ubiquitination mediated by gp78 and UBE2G2".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 42.5(2010):303-310. |
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