Phosphoglycerate mutase 1 regulates dNTP pool and promotes homologous recombination repair in cancer cells
文献类型：期刊论文
| 作者 | Qu, Jia1,2; Sun, Wenyi2; Zhong, Jie3; Lv, Hao2; Zhu, Mingrui2; Xu, Jun2; Jin, Nan2; Xie, Zuoquan2 ; Tan, Minjia2; Lin, Shu-Hai3
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| 刊名 | JOURNAL OF CELL BIOLOGY
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| 出版日期 | 2017-02 |
| 卷号 | 216期号:2页码:409-424 |
| ISSN号 | 0021-9525 |
| DOI | 10.1083/jcb.201607008 |
| 文献子类 | Article |
| 英文摘要 | Glycolytic enzymes are known to play pivotal roles in cancer cell survival, yet their molecular mechanisms remain poorly understood. Phosphoglycerate mutase 1 (PGAM1) is an important glycolytic enzyme that coordinates glycolysis, pentose phosphate pathway, and serine biosynthesis in cancer cells. Herein, we report that PGAM1 is required for homologous recombination (HR) repair of DNA double-strand breaks (DSBs) caused by DNA-damaging agents. Mechanistically, PGAM1 facilitates DSB end resection by regulating the stability of CTBP-interacting protein (CtIP). Knockdown of PGAM1 in cancer cells accelerates CtIP degradation through deprivation of the intracellular deoxyribonucleotide triphosphate pool and associated activation of the p53/p73 pathway. Enzymatic inhibition of PGAM1 decreases CtIP protein levels, impairs HR repair, and hence sensitizes BRCA1/2-proficient breast cancer to poly(ADP-ribose) polymerase (PARP) inhibitors. Together, this study identifies a metabolically dependent function of PGAM1 in promoting HR repair and reveals a potential therapeutic opportunity for PGAM1 inhibitors in combination with PARP inhibitors. |
| WOS关键词 | DNA-DAMAGE ; BREAST-CANCER ; 6-PHOSPHOGLUCONATE DEHYDROGENASE ; RIBONUCLEOTIDE REDUCTASE ; HISTONE ACETYLATION ; CELLULAR-METABOLISM ; CTIP ; P73 ; PHOSPHORYLATION ; SUPPRESSION |
| 资助项目 | China International Science and Technology Cooperation Program[2015DFM30040] ; National Science and Technology Major Project[2015ZX09101009] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020000] ; Natural Science Foundation of China for Innovation Research Group[81321092] ; Natural Science Foundation of China[81573464] ; Natural Science Foundation of China[21377106] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000394244800016 |
| 出版者 | ROCKEFELLER UNIV PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275646]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Ding, Jian; Huang, Min |
| 作者单位 | 1.Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Nanjing 210023, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Shanghai Jiao Tong Univ, Sch Med, Dept Biochem & Mol Cell Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Shanghai 200025, Peoples R China |
| 推荐引用方式 GB/T 7714 | Qu, Jia,Sun, Wenyi,Zhong, Jie,et al. Phosphoglycerate mutase 1 regulates dNTP pool and promotes homologous recombination repair in cancer cells[J]. JOURNAL OF CELL BIOLOGY,2017,216(2):409-424. |
| APA | Qu, Jia.,Sun, Wenyi.,Zhong, Jie.,Lv, Hao.,Zhu, Mingrui.,...&Huang, Min.(2017).Phosphoglycerate mutase 1 regulates dNTP pool and promotes homologous recombination repair in cancer cells.JOURNAL OF CELL BIOLOGY,216(2),409-424. |
| MLA | Qu, Jia,et al."Phosphoglycerate mutase 1 regulates dNTP pool and promotes homologous recombination repair in cancer cells".JOURNAL OF CELL BIOLOGY 216.2(2017):409-424. |
入库方式： OAI收割
来源：上海药物研究所
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