The novel cereblon modulator CC-885 inhibits mitophagy via selective degradation of BNIP3L
文献类型：期刊论文
| 作者 | Hao, Bing-bing1,2,3; Li, Xiao-jing4; Jia, Xing-long2,3,5; Wang, Yu-xing6; Zhai, Lin-hui1,2,3; Li, Duan-zhuo6; Liu, Jie6; Zhang, Die6; Chen, Yu-lu6; Xu, Yong-hu7 |
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2020-03-24 |
| 页码 | 9 |
| 关键词 | immunomodulatory drugs (IMiDs) CC-885 BNIP3L mitophagy CRBN acute myeloid leukemia mitochondria-targeting drugs |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/s41401-020-0367-9 |
| 通讯作者 | Liu, Bin(liubin3575630@163.com) ; Tan, Min-jia(mjtan@simm.ac.cn) |
| 英文摘要 | Mitophagy is a degradative pathway that mediates the degradation of the entire mitochondria, and defects in this process are implicated in many diseases including cancer. In mammals, mitophagy is mediated by BNIP3L (also known as NIX) that is a dual regulator of mitochondrial turnover and programmed cell death pathways. Acute myeloid leukemia (AML) cells with deficiency of BNIP3L are more sensitive to mitochondria-targeting drugs. But small molecular inhibitors for BNIP3L are currently not available. Some immunomodulatory drugs (IMiDs) have been proved by FDA for hematologic malignancies, however, the underlining molecular mechanisms are still elusive, which hindered the applications of BNIP3L inhibition for AML treatment. In this study we carried out MS-based quantitative proteomics analysis to identify the potential neosubstrates of a novel thalidomide derivative CC-885 in A549 cells. In total, we quantified 5029 proteins with 36 downregulated in CRBN+/+ cell after CC-885 administration. Bioinformatic analysis showed that macromitophagy pathway was enriched in the negative pathway after CC-885 treatment. We further found that CC-885 caused both dose- and time-dependent degradation of BNIP3L in CRBN+/+, but not CRBN-/- cell. Thus, our data uncover a novel role of CC-885 in the regulation of mitophagy by targeting BNIP3L for CRL4CRBN E3 ligase-dependent ubiquitination and degradation, suggesting that CC-885 could be used as a selective BNIP3L degradator for the further investigation. Furthermore, we demonstrated that CC-885 could enhance AML cell sensitivity to the mitochondria-targeting drug rotenone, suggesting that combining CC-885 and mitochondria-targeting drugs may be a therapeutic strategy for AML patients. |
| WOS关键词 | LENALIDOMIDE ; EXPRESSION ; PROMOTES ; STRATEGY |
| 资助项目 | National Natural Science Foundation of China[81872888] ; National Natural Science Foundation of China[91753203] ; National Natural Science Foundation of China[81773018] ; Natural Science Foundation of China for Innovation Research Group[81821005] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program[2018ZX09711002-004] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000521522200001 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/280914]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Liu, Bin; Tan, Min-jia |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Chem Prote Ctr, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Fudan Univ, Shanghai Med Coll, Dept Biochem & Mol Biol, Key Lab Metab & Mol Med,Minist Educ, Shanghai 200030, Peoples R China 5.Shanghai Univ, Sch Life Sci, Lab Noncoding RNA & Canc, Shanghai 200444, Peoples R China 6.Hubei Polytech Univ, Sch Med, Hubei Key Lab Kidney Dis Pathogenesis & Intervent, Huangshi 435003, Hubei, Peoples R China 7.Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Pediat Urol, 1665 Kongjiang St, Shanghai 200092, Peoples R China 8.Kyungpook Natl Univ, Coll Pharm, Plus KNU Multiom Based Creat Drug Res Team, BK21, Daegu 41566, South Korea 9.Kyungpook Natl Univ, Res Inst Pharmaceut Sci, Daegu 41566, South Korea 10.Chinese Acad Sci, Shanghai Inst Mat Med, Synthet Organ & Med Chem Lab, Key Lab Receptor Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hao, Bing-bing,Li, Xiao-jing,Jia, Xing-long,et al. The novel cereblon modulator CC-885 inhibits mitophagy via selective degradation of BNIP3L[J]. ACTA PHARMACOLOGICA SINICA,2020:9. |
| APA | Hao, Bing-bing.,Li, Xiao-jing.,Jia, Xing-long.,Wang, Yu-xing.,Zhai, Lin-hui.,...&Tan, Min-jia.(2020).The novel cereblon modulator CC-885 inhibits mitophagy via selective degradation of BNIP3L.ACTA PHARMACOLOGICA SINICA,9. |
| MLA | Hao, Bing-bing,et al."The novel cereblon modulator CC-885 inhibits mitophagy via selective degradation of BNIP3L".ACTA PHARMACOLOGICA SINICA (2020):9. |
入库方式： OAI收割
来源：上海药物研究所
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