FOXO3相关信号途径影响细胞自噬的研究进展
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摘要
叉形头转录因子O亚型3(FOXO3)是FOXO家族的重要成员,其广泛参与机体的许多生物学过程,如细胞自噬、氧化应激反应、细胞周期调控及细胞凋亡,但具体的调控机制尚未明确。FOXO3参与自噬调控的活性受磷酸化及乙酰化等修饰的影响,并多与AMP活化的蛋白激酶、磷脂酰肌醇-3-激酶/蛋白激酶B等信号转导通路相关。此外,FOXO3还通过调节一些自噬相关基因如微管相关蛋白1轻链3、磷脂酰肌醇-3-激酶/囊泡蛋白分选相关蛋白34、γ氨基丁酸受体相关蛋白1等的转录调控自噬。因此,了解转录因子FOXO3在自噬调节中的作用有助于对经典自噬模型进行探究,也可对自噬相关疾病如肿瘤、衰老以及神经退行性变,包括帕金森病、阿尔茨海默病等疾病的治疗提供线索。
Forkhead box O 3( FOXO3) is a key member of FOXO family. It extensively participates in many biological processes,such as cell autophagy,oxidative stress response,cell cycle control and cell apoptosis of organism,but its specific regulatory mechanism is still unknown. FOXO3' s activity of participating in autophagy regulation is impacted by modifications,such as phosphorylation and acetylation,and it often relates to signal transduction pathways,such as AMP-activated protein kinase and phosphatidylinositol-3 kinase/protein kinase B. Besides,FOXO3 also regulates autophagy through regulating the transcription of some autophagy-related genes,such as microtubule-associated protein 1 light chain 3,phosphatidylinositol 3 kinase/vesicle protein sorting associated protein 34,γ-aminobutyric acid receptor-associated protein 1. Thus,understanding of the transcription factor-FOXO3' s action in autophagy regulation not only contributes to the research on classical autophagy model,but also provides clues to the treatment of autophagy-related diseases,such as tumor,senility and neurodegeneration,including Parkinson's disease,Alzheimer's disease,etc.
Forkhead box O 3( FOXO3) is a key member of FOXO family. It extensively participates in many biological processes,such as cell autophagy,oxidative stress response,cell cycle control and cell apoptosis of organism,but its specific regulatory mechanism is still unknown. FOXO3' s activity of participating in autophagy regulation is impacted by modifications,such as phosphorylation and acetylation,and it often relates to signal transduction pathways,such as AMP-activated protein kinase and phosphatidylinositol-3 kinase/protein kinase B. Besides,FOXO3 also regulates autophagy through regulating the transcription of some autophagy-related genes,such as microtubule-associated protein 1 light chain 3,phosphatidylinositol 3 kinase/vesicle protein sorting associated protein 34,γ-aminobutyric acid receptor-associated protein 1. Thus,understanding of the transcription factor-FOXO3' s action in autophagy regulation not only contributes to the research on classical autophagy model,but also provides clues to the treatment of autophagy-related diseases,such as tumor,senility and neurodegeneration,including Parkinson's disease,Alzheimer's disease,etc.
引文
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[26]Chen S,Han Q,Wang X,et al.IBP-mediated suppression of autophagy promotes growth and metastasis of breast cancer cells via activating m TORC2/Akt/FOXO3a signaling pathway[J].Cell Death Dis,2013,4:e842.
[27]Luo L,Lu AM,Wang Y,et al.Chronic resistance training activates autophagy and reduces apoptosis of muscle cells by modulating IGF-1 and its receptors,Akt/m TOR and Akt/FOXO3a signaling in aged rats[J].Exp Gerontol,2013,48(4):427-436.
[28]Paula-Gomes S,Gon9alves DA,Baviera AM,et al.Insulin suppresses atrophy-and autophagy-related genes in heart tissue and cardiomyocytes through AKT/FOXO signaling[J].Horm Metab Res,2013,45(12):849-855.
[29]Li C,Wang Z,Wang C,et al.Perivascular adipose tissue-derived adiponectin inhibits collar-induced carotid atherosclerosis by promoting macrophage autophagy[J].PLo S One,2015,10(5):e0124031.
[30]Lang F,Voelkl J.Therapeutic potential of serum and glucocorticoid inducible kinase inhibition[J].Expert Opin Investig Drugs,2013,22(6):701-714.
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[32]Jiang T,Yu JT,Zhu XC,et al.Ischemic preconditioning provides neuroprotection by induction of AMP-activated protein kinasedependent autophagy in a rat model of ischemic stroke[J].Mol Neurobiol,2015,51(1):220-229.
[33]Jain N,Mishra R,Ganesh S.Fox O3a-mediated autophagy is downregulated in the laforin deficient mice,an animal model for Lafora progressive myoclonus epilepsy[J].Biochem Biophys Res Commun,2016,474(2):321-327.
[34]Deng Y,Xiao Y,Yuan F,et al.SGK1/FOXO3 signaling in hypothalamic POMC neurons mediates glucocorticoid-increased adiposity[J].Diabetes,2018,67(4):569-580.
[35]刘伟伟.SGK1在前列腺癌中的作用及其机制研究[D].杭州:浙江大学,2018.
[36]Menzies FM,Fleming A,Caricasole A,et al.Autophagy and neurodegeneration:Pathogenic mechanisms and therapeutic opportunities[J].Neuron,2017,93(5):1015-1034.
[37]Xie Y,Jiang D,Xiao J,et al.Ischemic preconditioning attenuates ischemia/reperfusion-induced kidney injury by activating autophagy via the SGK1 signaling pathway[J].Cell Death Dis,2018,9(3):338.
[38]Pino E,Amamoto R,Zheng L,et al.FOXO3 determines the accumulation ofα-synuclein and controls the fate of dopaminergic neurons in the substantia nigra[J].Hum Mol Genet,2014,23(6):1435-1452.
[39]Choe YJ,Ha TJ,Ko KW,et al.Anthocyanins in the black soybean(Glycine max L.)protect U2OS cells from apoptosis by inducing autophagy via the activation of adenosyl monophosphate-dependent protein kinase[J].Oncol Rep,2012,28(6):2049-2056.
[40]Liu YM,Lv J,Zeng QL,et al.AMPK activation ameliorates D-GalN/LPS-induced acute liver failure by upregulating Foxo3Ato induce autophagy[J].Exp Cell Res,2017,358(2):335-342.
[41]Zhang M,Zhu H,Ding Y,et al.AMP-activated protein kinaseα1promotes atherogenesis by increasing monocyte-to-macrophage differentiation[J].J Biol Chem,2017,292(19):7888-7903.
[42]Zhang SF,Zhang Y,Li B,et al.Physical inactivity induces the atrophy of skeletal muscle of rats through activating AMPK/FOXO3 signal pathway[J].Eur Rev Med Pharmacol Sci,2018,22(1):199-209.
[43]Czarny P,Pawlowska E,Bialkowska-Warzecha J,et al.Autophagy in DNA damage response[J].Int J Mol Sci,2015,16(2):2641-2662.
[2]He C,Klionsky DJ.Regulation mechanisms and signaling pathways of autophagy[J].Annu Rev Genet,2009,43:67-93.
[3]Bánréti A,Sass M,Graba Y.The emerging role of acetylation in the regulation of autophagy[J].Autophagy,2013,9(6):819-829.
[4]Shin HR,Kim H,Kim KI,et al.Epigenetic and transcriptional regulation of autophagy[J].Autophagy,2016,12(11):2248-2249.
[5]Donlon TA,Morris BJ,Chen R,et al.FOXO3 longevity interactome on chromosome 6[J].Aging Cell,2017,16(5):1016-1025.
[6]Broer L,Buchman AS,Deelen J,et al.GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy[J].J Gerontol A Biol Sci Med Sci,2015,70(1):110-118.
[7]Tsai KL,Sun YJ,Huang CY,et al.Crystal structure of the human FOXO3a-DBD/DNA complex suggests the effects of post-translational modification[J].Nucleic Acids Res,2007,35(20):6984-6994.
[8]Senf SM,Sandesara PB,Reed SA,et al.p300 Acetyltransferase activity differentially regulates the localization and activity of the FOXO homologues in skeletal muscle[J].Am J Physiol Cell Physiol,2011,300(6):C1490-1501.
[9]Byun SO,Zhou H,Hickford JG.Characterization of genetic variation in the Forkhead box class O3 gene(FOXO3)in sheep[J].DNA Cell Biol,2011,30(7):449-452.
[10]Li L,Zviti R,Ha C,et al.Forkhead box O3(Fox O3)regulates kidney tubular autophagy following urinary tract obstruction[J].J Biol Chem,2017,292(33):13774-13783.
[11]Nakatogawa H,Suzuki K,Kamada Y,et al.Dynamics and diversity in autophagy mechanisms:Lessons from yeast[J].Nat Rev Mol Cell Biol,2009,10(7):458-467.
[12]Klionsky DJ.Autophagy:From phenomenology to molecular understanding in less than a decade[J].Nat Rev Mol Cell Biol,2007,8(11):931-937.
[13]Klionsky DJ,Abdelmohsen K,Abe A,et al.Guidelines for the use and interpretation of assays for monitoring autophagy(3rd edition)[J].Autophagy,2016,12(1):1-222.
[14]Efeyan A,Zoncu R,Sabatini DM.Amino acids and m TORC1:From lysosomes to disease[J].Trends Mol Med,2012,18(9):524-533.
[15]Alemu EA,Lamark T,Torgersen KM,et al.ATG8 family proteins act as scaffolds for assembly of the ULK complex:Sequence requirements for LC3-interacting region(LIR)motifs[J].J Biol Chem,2012,287(47):39275-39290.
[16]Wirth M,Joachim J,Tooze SA.Autophagosome formation--the role of ULK1 and Beclin1-PI3KC3 complexes in setting the stage[J].Semin Cancer Biol,2013,23(5):301-309.
[17]Wani WY,Boyer-Guittaut M,Dodson M,et al.Regulation of autophagy by protein post-translational modification[J].Lab Invest,2015,95(1):14-25.
[18]Mammucari C,Milan G,Romanello V,et al.Fox O3 controls autophagy in skeletal muscle in vivo[J].Cell Metab,2007,6(6):458-471.
[19]Zhao J,Brault JJ,Schild A,et al.Fox O3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells[J].Cell Metab,2007,6(6):472-483.
[20]Cao DJ,Jiang N,Blagg A,et al.Mechanical unloading activates Fox O3 to trigger Bnip3-dependent cardiomyocyte atrophy[J].J Am Heart Assoc,2013,2(2):e000016.
[21]Sengupta A,Molkentin JD,Yutzey KE.Fox O transcription factors promote autophagy in cardiomyocytes[J].J Biol Chem,2009,284(41):28319-28331.
[22]Chi Y,Shi C,Zhao Y,et al.Forkhead box O(FOXO)3 modulates hypoxia-induced autophagy through AMPK signalling pathway in cardiomyocytes[J].Biosci Rep,2016,36(3):pii:e00345.
[23]Gonzalez E,Mc Graw TE.The Akt kinases:Isoform specificity in metabolism and cancer[J].Cell Cycle,2009,8(16):2502-2508.
[24]钱帅伟,丁树哲.运动性细胞自噬是调节骨骼肌代谢稳态的内置机制[J].体育科学,2015,35(10):55-65.
[25]van der Vos KE,Eliasson P,Proikas-Cezanne T,et al.Modulation of glutamine metabolism by the PI(3)K-PKB-FOXO network regulates autophagy[J].Nat Cell Biol,2012,14(8):829-837.
[26]Chen S,Han Q,Wang X,et al.IBP-mediated suppression of autophagy promotes growth and metastasis of breast cancer cells via activating m TORC2/Akt/FOXO3a signaling pathway[J].Cell Death Dis,2013,4:e842.
[27]Luo L,Lu AM,Wang Y,et al.Chronic resistance training activates autophagy and reduces apoptosis of muscle cells by modulating IGF-1 and its receptors,Akt/m TOR and Akt/FOXO3a signaling in aged rats[J].Exp Gerontol,2013,48(4):427-436.
[28]Paula-Gomes S,Gon9alves DA,Baviera AM,et al.Insulin suppresses atrophy-and autophagy-related genes in heart tissue and cardiomyocytes through AKT/FOXO signaling[J].Horm Metab Res,2013,45(12):849-855.
[29]Li C,Wang Z,Wang C,et al.Perivascular adipose tissue-derived adiponectin inhibits collar-induced carotid atherosclerosis by promoting macrophage autophagy[J].PLo S One,2015,10(5):e0124031.
[30]Lang F,Voelkl J.Therapeutic potential of serum and glucocorticoid inducible kinase inhibition[J].Expert Opin Investig Drugs,2013,22(6):701-714.
[31]Lang F,Stournaras C.Serum and glucocorticoid inducible kinase,metabolic syndrome,inflammation,and tumor growth[J].Hormones(Athens),2013,12(2):160-171.
[32]Jiang T,Yu JT,Zhu XC,et al.Ischemic preconditioning provides neuroprotection by induction of AMP-activated protein kinasedependent autophagy in a rat model of ischemic stroke[J].Mol Neurobiol,2015,51(1):220-229.
[33]Jain N,Mishra R,Ganesh S.Fox O3a-mediated autophagy is downregulated in the laforin deficient mice,an animal model for Lafora progressive myoclonus epilepsy[J].Biochem Biophys Res Commun,2016,474(2):321-327.
[34]Deng Y,Xiao Y,Yuan F,et al.SGK1/FOXO3 signaling in hypothalamic POMC neurons mediates glucocorticoid-increased adiposity[J].Diabetes,2018,67(4):569-580.
[35]刘伟伟.SGK1在前列腺癌中的作用及其机制研究[D].杭州:浙江大学,2018.
[36]Menzies FM,Fleming A,Caricasole A,et al.Autophagy and neurodegeneration:Pathogenic mechanisms and therapeutic opportunities[J].Neuron,2017,93(5):1015-1034.
[37]Xie Y,Jiang D,Xiao J,et al.Ischemic preconditioning attenuates ischemia/reperfusion-induced kidney injury by activating autophagy via the SGK1 signaling pathway[J].Cell Death Dis,2018,9(3):338.
[38]Pino E,Amamoto R,Zheng L,et al.FOXO3 determines the accumulation ofα-synuclein and controls the fate of dopaminergic neurons in the substantia nigra[J].Hum Mol Genet,2014,23(6):1435-1452.
[39]Choe YJ,Ha TJ,Ko KW,et al.Anthocyanins in the black soybean(Glycine max L.)protect U2OS cells from apoptosis by inducing autophagy via the activation of adenosyl monophosphate-dependent protein kinase[J].Oncol Rep,2012,28(6):2049-2056.
[40]Liu YM,Lv J,Zeng QL,et al.AMPK activation ameliorates D-GalN/LPS-induced acute liver failure by upregulating Foxo3Ato induce autophagy[J].Exp Cell Res,2017,358(2):335-342.
[41]Zhang M,Zhu H,Ding Y,et al.AMP-activated protein kinaseα1promotes atherogenesis by increasing monocyte-to-macrophage differentiation[J].J Biol Chem,2017,292(19):7888-7903.
[42]Zhang SF,Zhang Y,Li B,et al.Physical inactivity induces the atrophy of skeletal muscle of rats through activating AMPK/FOXO3 signal pathway[J].Eur Rev Med Pharmacol Sci,2018,22(1):199-209.
[43]Czarny P,Pawlowska E,Bialkowska-Warzecha J,et al.Autophagy in DNA damage response[J].Int J Mol Sci,2015,16(2):2641-2662.