O-GlcNAcylation of fumarase maintains tumour growth under glucose deficiency
文献类型：期刊论文
| 作者 | Wang, Ting2,3; Yu, Qiujing3; Li, Jingjie3; Hu, Bin2,3; Zhao, Qin3; Ma, Chunmin3; Huang, Wenhua3; Zhuo, Lingang3; Jiang, Yuhui2,3; Fang, Houqin4 |
| 刊名 | NATURE CELL BIOLOGY
 |
| 出版日期 | 2017 |
| 卷号 | 19期号:7页码:833-+ |
| 关键词 | allele-specific expression colorectal cancer cis-regulatory variation somatic mutation tumor |
| ISSN号 | 1465-7392 |
| DOI | 10.1038/ncb3562 |
| 文献子类 | Article |
| 英文摘要 | Chromatin-associated fumarase (FH) affects histone methylation via its metabolic activity. However, whether this effect is involved in gene transcription remains to be clarified. In this study, we show that under glucose deprivation conditions, AMPK phosphorylates FH at Ser75, which in turn forms a complex with ATF2 and participates in promoter activation. FH-catalysed fumarate in promoter regions inhibits KDM2A demethylase activity, and thus maintains the H3K36me2 profile and facilitates gene expression for cell growth arrest. On the other hand, FH is found to be O-GlcNAcylated at the AMPK phosphorylation site; FH-ATF2-mediated downstream events are impeded by FH O-GlcNAcylation, especially in cancer cells that display robust O-GlcNAc transferase (OGT) activity. Consistently, the FH-Ser75 phosphorylation level inversely correlates with the OGT level and poor prognosis in pancreatic cancer patients. These findings uncover a previously uncharacterized mechanism underlying transcription regulation by FH and the linkage between dysregulated OGT activity and growth advantage of cancer cells under glucose deficiency. |
| 学科主题 | Cell Biology |
| WOS关键词 | ACTIVATING TRANSCRIPTION FACTOR-2 ; RIBOSOMAL-RNA TRANSCRIPTION ; PANCREATIC-CANCER ; GENE-EXPRESSION ; DNA-REPAIR ; METABOLISM ; DEMETHYLATION ; INHIBITION ; HISTONE ; CELLS |
| 语种 | 英语 |
| WOS记录号 | WOS:000404408800015 |
| 出版者 | NATURE PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/943]  |
| 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.Shanghai Jiao Tong Univ, Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Stem Cell Biol,Inst Hlth Sci,Sch Med, 320 Yueyang Rd, Shanghai 200031, Peoples R China, 2.Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Gastroenterol, Shanghai 200080, Peoples R China; 3.Shanghai Jiao Tong Univ, Inst Cell Metab, Shanghai Gen Hosp, Shanghai Key Lab Pancreat Dis,Sch Med, Shanghai 200080, Peoples R China; 4.East China Normal Univ, Shanghai Key Lab Regulatory Biol, Sch Life Sci, Shanghai 200241, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wang, Ting,Yu, Qiujing,Li, Jingjie,et al. O-GlcNAcylation of fumarase maintains tumour growth under glucose deficiency[J]. NATURE CELL BIOLOGY,2017,19(7):833-+. |
| APA | Wang, Ting.,Yu, Qiujing.,Li, Jingjie.,Hu, Bin.,Zhao, Qin.,...&,.(2017).O-GlcNAcylation of fumarase maintains tumour growth under glucose deficiency.NATURE CELL BIOLOGY,19(7),833-+. |
| MLA | Wang, Ting,et al."O-GlcNAcylation of fumarase maintains tumour growth under glucose deficiency".NATURE CELL BIOLOGY 19.7(2017):833-+. |
入库方式： OAI收割
来源：上海营养与健康研究所
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