Profiling human protein degradome delineates cellular responses to proteasomal inhibition and reveals a feedback mechanism in regulating proteasome homeostasis
文献类型：期刊论文
| 作者 | Yu, T; Tao, YH; Yang, MQ; Chen, P; Gao, XB; Zhang, YB; Zhang, T; Chen, Z; Hou, J; Zhang, Y |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2014 |
| 卷号 | 24期号:10页码:1214-1230 |
| 关键词 | bortezomib combination therapy proteostasis protein degradome proteasome homeostasis N-end rule ubiquitin |
| 通讯作者 | Hu, RG (reprint author), Univ Chinese Acad Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,shmuzt@126.com ; drchenzi@163.com ; coryhu@sibs.ac.cn |
| 英文摘要 | Global change in protein turnover (protein degradome) constitutes a central part of cellular responses to intrinsic or extrinsic stimuli. However, profiling protein degradome remains technically challenging. Recently, inhibition of the proteasome, e. g., by using bortezomib (BTZ), has emerged as a major chemotherapeutic strategy for treating multiple myeloma and other human malignancies, but systematic understanding of the mechanisms for BTZ drug action and tumor drug resistance is yet to be achieved. Here we developed and applied a dual-fluorescence-based Protein Turnover Assay (ProTA) to quantitatively profile global changes in human protein degradome upon BTZ-induced proteasomal inhibition. ProTA and subsequent network analyses delineate potential molecular basis for BTZ action and tumor drug resistance in BTZ chemotherapy. Finally, combined use of BTZ with drugs targeting the ProTA-identified key genes or pathways in BTZ action reduced BTZ resistance in multiple myeloma cells. Remarkably, BTZ stabilizes proteasome subunit PSMC1 and proteasome assembly factor PSMD10, suggesting a previously under-appreciated mechanism for regulating proteasome homeostasis. Therefore, ProTA is a novel tool for profiling human protein degradome to elucidate potential mechanisms of drug action and resistance, which might facilitate therapeutic development targeting proteostasis to treat human disorders. |
| 学科主题 | Cell Biology |
| 类目[WOS] | Cell Biology |
| 关键词[WOS] | END RULE PATHWAY ; MULTIPLE-MYELOMA ; IN-VIVO ; BORTEZOMIB RESISTANCE ; UBIQUITIN LIGASES ; MAMMALIAN-CELLS ; NEXT-GENERATION ; 26S PROTEASOME ; CANCER ; DEGRADATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000344993300010 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/233]  |
| 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 | Yu, T,Tao, YH,Yang, MQ,et al. Profiling human protein degradome delineates cellular responses to proteasomal inhibition and reveals a feedback mechanism in regulating proteasome homeostasis[J]. CELL RESEARCH,2014,24(10):1214-1230. |
| APA | Yu, T.,Tao, YH.,Yang, MQ.,Chen, P.,Gao, XB.,...&Hu, RG.(2014).Profiling human protein degradome delineates cellular responses to proteasomal inhibition and reveals a feedback mechanism in regulating proteasome homeostasis.CELL RESEARCH,24(10),1214-1230. |
| MLA | Yu, T,et al."Profiling human protein degradome delineates cellular responses to proteasomal inhibition and reveals a feedback mechanism in regulating proteasome homeostasis".CELL RESEARCH 24.10(2014):1214-1230. |
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