Protein disulfide isomerase blocks the interaction of LC3II-PHB2 and promotes mTOR signaling to regulate autophagy and radio/chemo-sensitivity
文献类型:期刊论文
作者 | Wang, Ruru2,3; Shang, Yajing2,4; Chen, Bin2,3; Xu, Feng2,3; Zhang, Jie2,3; Zhang, Zhaoyang2,3; Zhao, Xipeng2,5; Wan, Xiangbo1; Xu, An2; Wu, Lijun2,5 |
刊名 | CELL DEATH & DISEASE |
出版日期 | 2022-10-06 |
卷号 | 13 |
ISSN号 | 2041-4889 |
DOI | 10.1038/s41419-022-05302-w |
通讯作者 | Zhao, Guoping(gpz@ipp.ac.cn) |
英文摘要 | Protein disulfide isomerase (PDI) is an endoplasmic reticulum (ER) enzyme that mediates the formation of disulfide bonds, and is also a therapeutic target for cancer treatment. Our previous studies found that PDI mediates apoptotic signaling by inducing mitochondrial dysfunction. Considering that mitochondrial dysfunction is a major contributor to autophagy, how PDI regulates autophagy remains unclear. Here, we provide evidence that high expression of PDI in colorectal cancer tumors significantly increases the risk of metastasis and poor prognosis of cancer patients. PDI inhibits radio/chemo-induced cell death by regulating autophagy signaling. Mechanistically, the combination of PDI and GRP78 was enhanced after ER stress, which inhibits the degradation of AKT by GRP78, and eventually activates the mTOR pathway to inhibit autophagy initiation. In parallel, PDI can directly interact with the mitophagy receptor PHB2 in mitochondrial, then competitively blocks the binding of LC3II and PHB2 and inhibits the mitophagy signaling. Collectively, our results identify that PDI can reduce radio/chemo-sensitivity by regulating autophagy, which could be served as a potential target for radio/chemo-therapy. |
WOS关键词 | ENDOPLASMIC-RETICULUM STRESS ; ER STRESS ; DNA-REPAIR ; INHIBITION ; RESISTANCE ; GLIOBLASTOMA ; EXPRESSION ; GRP78/BIP ; DISCOVERY ; CHAPERONE |
资助项目 | National Natural Science Foundation of China[31870845] ; National Natural Science Foundation of China[12122510] ; National Natural Science Foundation of China[32171240] ; National Natural Science Foundation of China[11835014] ; Anhui Provincial Key RD Programm[202104a07020006] ; HFIPS Director's Fund[BJPY2021B07] ; HFIPS Director's Fund[YZJJZX202014] |
WOS研究方向 | Cell Biology |
语种 | 英语 |
出版者 | SPRINGERNATURE |
WOS记录号 | WOS:000864661900002 |
资助机构 | National Natural Science Foundation of China ; Anhui Provincial Key RD Programm ; HFIPS Director's Fund |
源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/129321] |
专题 | 中国科学院合肥物质科学研究院 |
通讯作者 | Zhao, Guoping |
作者单位 | 1.Sun Yat Sen Univ, Affiliated Hosp 6, Guangzhou 510275, Guangdong, Peoples R China 2.Chinese Acad Sci, Key Lab High Magnet Field & Ion Beam Phys Biol, Anhui Prov Key Lab Environm Toxicol & Pollut Cont, High Magnet Field Lab,Hefei Inst Phys Sci, Hefei 230031, Anhui, Peoples R China 3.Univ Sci & Technol China, Hefei 230026, Anhui, Peoples R China 4.Anhui Med Univ, Hefei 230032, Anhui, Peoples R China 5.Anhui Univ, Informat Mat & Intelligent Sensing Lab Anhui Prov, Inst Phys Sci & Informat Technol, Hefei 230601, Anhui, Peoples R China |
推荐引用方式 GB/T 7714 | Wang, Ruru,Shang, Yajing,Chen, Bin,et al. Protein disulfide isomerase blocks the interaction of LC3II-PHB2 and promotes mTOR signaling to regulate autophagy and radio/chemo-sensitivity[J]. CELL DEATH & DISEASE,2022,13. |
APA | Wang, Ruru.,Shang, Yajing.,Chen, Bin.,Xu, Feng.,Zhang, Jie.,...&Zhao, Guoping.(2022).Protein disulfide isomerase blocks the interaction of LC3II-PHB2 and promotes mTOR signaling to regulate autophagy and radio/chemo-sensitivity.CELL DEATH & DISEASE,13. |
MLA | Wang, Ruru,et al."Protein disulfide isomerase blocks the interaction of LC3II-PHB2 and promotes mTOR signaling to regulate autophagy and radio/chemo-sensitivity".CELL DEATH & DISEASE 13(2022). |
入库方式: OAI收割
来源:合肥物质科学研究院
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