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2021, 27, v.61 102-105
PI3K/AKT/mTOR信号通路在细胞自噬中作用及机制的研究进展
基金项目(Foundation): 云南省医学学科带头人项目(D2018028)
邮箱(Email): WeiXuzxc@163.com;
DOI:
摘要:

细胞自噬是一种吞噬自身细胞质蛋白或细胞器使其包被进入囊泡催化分解的循环过程,细胞以此获得它们的大分子前体。磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路与细胞自噬反应之间存在着密切关系。PI3Kα催化亚基通过NF-E2 P45相关因子2-抗氧化剂反应元件依赖的途径及激活AKT蛋白对细胞自噬起抑制作用,相反,PI3Kβ催化亚基通过与RAS相关蛋白5结合及激活叉头盒蛋白O(FoxO)对细胞自噬起促进作用。AKT通过激活mTORC1和抑制FoxO及细胞自噬相关基因(ATG)的表达对细胞自噬起抑制作用。mTOR1通过磷酸化Unc-51样激酶复合体、ATG13、ATG14、蛋白质核受体结合因子2等及与细胞自噬小体的形成和成熟过程相关的蛋白以及调控转录因子EB/转录因子E3的活性对细胞自噬起抑制作用,mTORC2既可以通过丝氨酸/苏氨酸蛋白激酶sgk1蛋白抑制细胞自噬,又可以通过上调线粒体膜外电压依赖性阴离子选择通道蛋白1的表达促进细胞自噬。

Abstract:

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参考文献

[1]LEVY J M M,TOWERS C G,THORBURN A.Targeting autophagy in cancer[J].Nat Rev Cancer,2017,17(9):528-542.

[2]WU Z,WANG H,FANG S,et al.Roles of endoplasmic reticulum stress and autophagy on H2O2-induced oxidative stress injury in Hep G2 cells[J].Mol Med Rep,2018,18(5):4163-4174.

[3]BILANGES B,POSOR Y,VANHAESEBROECK B.PI3K isoforms in cell signalling and vesicle trafficking[J].Nat Rev Mol Cell Biol,2019,20(9):515-534.

[4]WANG H,LIU Y,WANG D,et al.The upstream pathway of m TOR-mediated autophagy in liver diseases[J].Cells,2019,8(12):1-36.

[5]WANG L,CHEN Y,STERNBERG P,et al.Essential roles of the PI3 kinase/Akt pathway in regulating Nrf2-dependent antioxidant functions in the RPE[J].Invest Ophthalmol Vis Sci,2008,49(4):1671-1678.

[6]LV H,YANG H,WANG Z,et al.Nrf2 signaling and autophagy are complementary in protecting lipopolysaccharide/d-galactosamine-induced acute liver injury by licochalcone A[J].Cell Death Dis,2019,10(4):1-15.

[7]JIANG T,HARDER B,ROJODE LAVEGA M,et al.p62 links autophagy and Nrf2 signaling[J].Free Radic Biol Med,2015,88(Pt B):199-204.

[8]YU X,LONG Y C,SHEN H M.Differential regulatory functions of three classes of phosphatidylinositol and phosphoinositide 3-kinases in autophagy[J].Autophagy,2015,11(10):1711-1728.

[9]DOU Z,PAN J A,DBOUK H A,et al.Class IA PI3K p110βsubunit promotes autophagy through Rab5 small GTPase in response to growth factor limitation[J].Mol Cell,2013,50(1):29-42.

[10]SHIN H J,KWON H K,LEE J H,et al.Etoposide induced cytotoxicity mediated by ROS and ERK in human kidney proximal tubule cells[J].Sci Rep,2016,6:1-13.

[11]SINGH P,DAR M S,DAR M J.p110αand p110βisoforms of PI3K signaling:are they two sides of the same coin[J].FEBSLett,2016,590(18):3071-3082.

[12]CHENG Z.The fox O-autophagy axis in health and disease[J].Trends Endocrinol Metab,2019,30(9):658-671.

[13]YOGEV O,GOLDBERG R,ANZI S,et al.Jun proteins are starvation-regulated inhibitors of autophagy[J].Cancer Res,2010,70(6):2318-2327.

[14]TAKEUCHI H,KONDO Y,FUJIWARA K,et al.Synergistic augmentation of rapamycin-induced autophagy in malignant glioma cells by phosphatidylinositol 3-kinase/protein kinase B inhibitors[J].Cancer Res,2005,65(8):3336-3346.

[15]NAZIO F,STRAPPAZZON F,ANTONIOLI M,et al.m TOR inhibits autophagy by controlling ULK1 ubiquitylation,self-association and function through AMBRA1 and TRAF6[J].Nat Cell Biol,2013,15(4):406-416.

[16]MA X,ZHANG S,HE L,et al.MTORC1-mediated NRBF2phosphorylation functions as a switch for the classⅢPtd Ins3Kand autophagy[J].Autophagy,2017,13(3):592-607.

[17]DOSSOU A S,BASU A.The emerging roles of m TORC1 in macromanaging autophagy[J].Cancers(Basel),2019,11(10):1-17.

[18]WAN W,LIU W.MTORC1 regulates autophagic membrane growth by targeting WIPI2[J].Autophagy,2019,15(4):742-743.

[19]ZHANG W,LI X,WANG S,et al.Regulation of TFEB activity and its potential as a therapeutic target against kidney diseases[J].Cell Death Discov,2020,6(32):1-10.

[20]COLLODET C,FORETZ M,DEAK M,et al.AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of m TOR[J].Faseb J,2019,33(11):12374-12391.

[21]ASPERNIG H,HEIMBUCHER T,QI W,et al.Mitochondrial perturbations couple m TORC2 to autophagy in C.elegans[J].Cell Rep,2019,29(6):1399-1409.

[22]WANG M,XUE Y,SHEN L,et al.Inhibition of SGK1 confers vulnerability to redox dysregulation in cervical cancer[J].Redox Biol,2019,24:1-15.

[23]HEIMBUCHER T,QI W,BAUMEISTER R.TORC2-SGK-1 signaling integrates external signals to regulate autophagic turnover of mitochondria via mt ROS[J].Autophagy,2020,16(6):1154-1156.

基本信息:

DOI:

中图分类号:R329.25

引用信息:

[1]施诚龙,陈冲,高永军等.PI3K/AKT/mTOR信号通路在细胞自噬中作用及机制的研究进展[J].山东医药,2021,61(27):102-105.

基金信息:

云南省医学学科带头人项目(D2018028)

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