Regulation of Ubiquitin-like with Plant Homeodomain and RING Finger Domain 1 (UHRF1) Protein Stability by Heat Shock Protein 90 Chaperone Machinery
文献类型：期刊论文
| 作者 | Ding, Guangjin3,4; Chen, Peilin3,4; Zhang, Hui3,4; Huang, Xiaojie1; Zang, Yi1 ; Li, Jiwen3,4; Li, Jia1; Wong, Jiemin2,3,4
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| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 出版日期 | 2016-09-16 |
| 卷号 | 291期号:38页码:20125-20135 |
| 关键词 | 70-kilodalton heat shock protein (HSP70) cancer therapy DNA methylation protein degradation ubiquitin |
| ISSN号 | 0021-9258 |
| DOI | 10.1074/jbc.M116.727214 |
| 文献子类 | Article |
| 英文摘要 | As a protein critical for DNA maintenance methylation and cell proliferation, UHRF1 is frequently highly expressed in various human cancers and is considered as a drug target for cancer therapy. In a high throughput screening for small molecules that induce UHRF1 protein degradation, we have identified the HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). We present evidence that UHRF1 interacts with HSP90 chaperone complex and is a novel HSP90 client protein. Pharmacological inhibition of HSP90 with 17-AAG or 17-dimethylaminoethylamino-17-demethoxygeldanamycin results in UHRF1 ubiquitination and proteasome-dependent degradation. Interestingly, this HSP90 inhibitor-induced UHRF1 degradation is independent of CHIP and CUL5, two previously identified ubiquitin E3 ligases for HSP90 client proteins. In addition, this degradation is dependent neither on the intrinsic E3 ligase of UHRF1 nor on the E3 ligase SCF-TRCP that has been implicated in regulation of UHRF1 stability. We also provide evidence that HSP90 inhibitors may suppress cancer cell proliferation in part through its induced UHRF1 degradation. Taken together, our results identify UHRF1 as a novel HSP90 client protein and shed light on the regulation of UHRF1 stability and function. |
| WOS关键词 | HEMI-METHYLATED DNA ; F-BOX PROTEINS ; BINDING-PROTEIN ; TRIAGE DECISIONS ; HSP90 INHIBITORS ; CLIENT PROTEINS ; CANCER-CELLS ; LUNG-CANCER ; LIGASE CHIP ; E3 LIGASE |
| 资助项目 | National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program" of China[2014ZX09507002-002] ; Ministry of Science and Technology of China[2015CB910402] ; National Natural Science Foundation of China[91419303] ; Science and Technology Commission of Shanghai Municipality[14XD1401700] ; Science and Technology Commission of Shanghai Municipality[11DZ2260300] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000383243100033 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/275888]  |
| 专题 | 国家新药筛选中心 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 药物安全性评价中心 |
| 通讯作者 | Li, Jia; Wong, Jiemin |
| 作者单位 | 1.Chinese Acad Sci, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 2.Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Guangdong, Peoples R China 3.East China Normal Univ, Shanghai Key Lab Regulatory Biol, Inst Biomed Sci, 500 Dongchuan Rd, Shanghai 200241, Peoples R China; 4.East China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Ding, Guangjin,Chen, Peilin,Zhang, Hui,et al. Regulation of Ubiquitin-like with Plant Homeodomain and RING Finger Domain 1 (UHRF1) Protein Stability by Heat Shock Protein 90 Chaperone Machinery[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2016,291(38):20125-20135. |
| APA | Ding, Guangjin.,Chen, Peilin.,Zhang, Hui.,Huang, Xiaojie.,Zang, Yi.,...&Wong, Jiemin.(2016).Regulation of Ubiquitin-like with Plant Homeodomain and RING Finger Domain 1 (UHRF1) Protein Stability by Heat Shock Protein 90 Chaperone Machinery.JOURNAL OF BIOLOGICAL CHEMISTRY,291(38),20125-20135. |
| MLA | Ding, Guangjin,et al."Regulation of Ubiquitin-like with Plant Homeodomain and RING Finger Domain 1 (UHRF1) Protein Stability by Heat Shock Protein 90 Chaperone Machinery".JOURNAL OF BIOLOGICAL CHEMISTRY 291.38(2016):20125-20135. |
入库方式： OAI收割
来源：上海药物研究所
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