蛋白质乙酰化修饰在细胞自噬中的作用进展
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摘要
蛋白质翻译后修饰与细胞自噬的关系是近几年来的研究热点.自噬的发生需要多类蛋白质协同完成.在此过程中,蛋白质的乙酰化修饰对细胞自噬起着十分重要的调节作用.本文就近年来的研究从两个角度进行了总结:一方面总结了蛋白质乙酰化修饰与自噬关系的功能性研究,主要涉及组蛋白、转录因子以及与乙酰辅酶A代谢过程中相关酶的研究进展;另一方面概括了细胞自噬过程中蛋白质乙酰化修饰组学的研究进展.乙酰化酶/去乙酰化酶是蛋白质乙酰化修饰水平的主要调控者,阐明酶与底物的关系将是深入探讨乙酰化修饰与细胞自噬关系的关键所在.这些研究结果必将为揭开细胞自噬机制提供理论基础.
The relationship between protein post-translational modification and autophagy has become a hot topic in recent years. A series of proteins are required to participate in the process of autophagy. Protein acetylation has been demonstrated to emerge as the main regulator to autophagy. In this paper, we reviewed related findings from two perspectives. On one hand, the role of protein acetylation on autophagy has been discussed, mainly including histones, transcription factors and most of enzymes to regulate the level of AcCoA.On the other hand, we presented the advancement with the acetylome profile in the process of autophagy.Acetylase and deacetylase are the main enzymes to be responsible for protein acetylation. The relationship between these enzymes and their substrates merited to be intensively investigated in the future studies. All of data would be very valuable to explore the mechanism with autophagy.
The relationship between protein post-translational modification and autophagy has become a hot topic in recent years. A series of proteins are required to participate in the process of autophagy. Protein acetylation has been demonstrated to emerge as the main regulator to autophagy. In this paper, we reviewed related findings from two perspectives. On one hand, the role of protein acetylation on autophagy has been discussed, mainly including histones, transcription factors and most of enzymes to regulate the level of AcCoA.On the other hand, we presented the advancement with the acetylome profile in the process of autophagy.Acetylase and deacetylase are the main enzymes to be responsible for protein acetylation. The relationship between these enzymes and their substrates merited to be intensively investigated in the future studies. All of data would be very valuable to explore the mechanism with autophagy.
引文
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[29]Chen Y,Zhao W,Yang J S,et al.Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.Mol Cell Proteomics,2012,11(10):1048-1062
[30]Rigbolt K T,Zarei M,Sprenger A,et al.Characterization of early autophagy signaling by quantitative phosphoproteomics.Autophagy,2014,10(2):356-371
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[33]Zhou Z.Characterization of the acetylome associated with rapamycin-induced autophagy[D].Hangzhou:Zhejiang University,2016
[34]Weinert BT,Narita T,Satpathy S,et al.Time-resolved analysis reveals rapid dynamics and broad scope of the CBP/p300acetylome.Cell,2018,174(1):231-244
[35]Lee I H,Finkel T.Regulation of autophagy by the p300acetyltransferase.J Biol Chem,2009,284(10):6322-6328
[36]Madeo F,Eisenberg T,Pietrocola F,et al.Spermidine in health and disease.Science,2018,359(6374):pii eaan2788
[37]Lee I H,Cao L,Mostoslavsky R,et al.A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy.Proc NatlAcad Sci USA.2008,105(9):3374-3379
[38]杨莉,肖凌,陈临溪.自噬与肺部疾病研究进展.生物化学与生物物理进展,2012,39(9):861-868Yang L,Xiao L,Chen L X.Prog Biochem Biophys,2012,39(9):861-868
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[40]谢凤,柳威,陈临溪.自噬参与心脏疾病调控的研究进展.生物化学与生物物理进展,2012,39(3):224-233Xie F,Liu W,Chen L X.Prog Biochem Biophys,2012,39(3):224-233
[2]Klionsky D J,Emr S D.Autophagy as a regulated pathway of cellular degradation.Science,2000,290(5497):1717-1721
[3]Deretic V.Autophagy as an immune defense mechanism.Curr Opin Immunol,2006,18(4):375-382
[4]Behrends C,Sowa ME,Gygi SP,et al.Network organization of the human autophagy system.Nature.2010,466(7302):68-76
[5]Deribe Y L,Pawson T,Dikic I.Post-translational modifications in signal integration.Nat Struct Mol Biol,2010,17(6):666-672
[6]Choudhary C,Kumar C,Gnad F,et al.Lysine acetylation targets protein complexes and co-regulates major cellular functions.Science,2009,325(5942):834-840
[7]Füllgrabe J,Lynch-Day M A,Heldring N,et al.The histone H4lysine 16 acetyltransferase h MOF regulates the outcome of autophagy.Nature,2013,500(7463):468-471
[8]Bernier M,Luo Y,Nwokelo K C,et al.Linker histone H1 and H3K56 acetylation are antagonistic regulators of nucleosome dynamics.Nat Commun,2015,6:10152
[9]Huang N,Liu Z,Zhu J,et al.Sirtuin 6 plays an oncogenic role and induces cell autophagy in esophageal cancer cells.Tumour Biol,2017,39(6):1010428317708532
[10]Park G,Tan J,Garcia G,et al.Regulation of histone acetylation by autophagy in Parkinson disease.J Biol Chem,2016,291(7):3531-3540
[11]Li X,Qian X,Lu Z.Local histone acetylation by ACSS2 promotes gene transcription for lysosomal biogenesis and autophagy.Autophagy,2017,13(10):1790-1791
[12]Matsuzaki H,Daitoku H,Hatta M,et al.Acetylation of Foxo1alters its DNA-binding ability and sensitivity to phosphorylation.Proc NatlAcad Sci USA,2005,102(32):11278-11283
[13]Zhao Y,Yang J,Liao W,et al.Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity.Nat Cell Biol,2010,12(7):665-675
[14]Zhang X,Cheng Q,Yin H,et al.Regulation of autophagy and EMTby the interplay between p53 and RAS during cancer progression.Int J Oncol,2017,51(1):18-24
[15]De U,Son J Y,Sachan R,et al.A new synthetic histone deacetylase inhibitor,MHY2256,induces apoptosis and autophagy cell death in endometrial cancer cells via p53 acetylation.Int J Mol Sci,2018,19(9):pii E2743
[16]Zhang J,Wang J,Zhou Z,et al.Importance of TFEB acetylation in control of its transcriptional activity and lysosomal function in response to histone deacetylase inhibitors.Autophagy,2018,14(6):1043-1059
[17]Marino G,Pietrocola F,Eisenberg T,et al.Regulation of autophagy by cytosolic acetyl-coenzyme A.Mol Cell,2014,53(5):710-725
[18]Zhao S,Xu W,Jiang W,et al.Regulation of cellular metabolism by protein lysine acetylation.Science.2010,327(5968):1000-1004
[19]Zhang Y,Xu Y Y,Yao C B,et al.Acetylation targets HSD17B4 for degradation via the CMA pathway in response to estrone.Autophagy,2017,13(3):538-553
[20]Qian X,Li X,Cai Q,et al.Phosphoglycerate kinase 1phosphorylates Beclin1 to induce autophagy.Mol Cell,2017,65(5):917-931
[21]Hu H,Zhu W,Qin J,et al.Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis.Hepatology,2017,65(2):515-528
[22]Lv L,Li D,Zhao D,et al.Acetylation targets the M2 isoform of pyruvate kinase for degradation through chaperone-mediated autophagy and promotes tumor growth.Mol Cell,2011,42(6):719-730
[23]Zhao D,Zou S W,Liu Y,et al.Lysine-5 acetylation negatively regulates lactate dehydrogenase A and is decreased in pancreatic cancer.Cancer Cell,2013,23(4):464-476
[24]Hebert A S,Dittenhafer-Reed K E,Yu W,et al.Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome.Mol Cell,2013,49(1):186-199
[25]Xie Y,Kang R,Sun X,et al.Posttranslational modification of autophagy-related proteins in macroautophagy.Autophagy,2015,11(1):28-45
[26]Liu M,Liang K,Zhen J,et al.Sirt6 deficiency exacerbates podocyte injury and proteinuria through targeting Notch signaling.Nat Commun,2017,8(1):413
[27]Lin S Y,Li T Y,Liu Q,et al.GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to autophagy.Science,2012,336(6080):477-481
[28]Nie T,Yang S,Ma H,et al.Regulation of ER stress-induced autophagy by GSK3β-TIP60-ULK1 pathway.Cell Death Dis,2016,7(12):e2563
[29]Chen Y,Zhao W,Yang J S,et al.Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.Mol Cell Proteomics,2012,11(10):1048-1062
[30]Rigbolt K T,Zarei M,Sprenger A,et al.Characterization of early autophagy signaling by quantitative phosphoproteomics.Autophagy,2014,10(2):356-371
[31]Harder L M,Bunkenborg J,Andersen J S.Inducing autophagy:a comparative phosphoproteomic study of the cellular response to ammonia and rapamycin.Autophagy,2014,10(2):339-355
[32]Morselli E,Mari?o G,Bennetzen M V,et al.Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome.J Cell Biol,2011,192(4):615-629
[33]Zhou Z.Characterization of the acetylome associated with rapamycin-induced autophagy[D].Hangzhou:Zhejiang University,2016
[34]Weinert BT,Narita T,Satpathy S,et al.Time-resolved analysis reveals rapid dynamics and broad scope of the CBP/p300acetylome.Cell,2018,174(1):231-244
[35]Lee I H,Finkel T.Regulation of autophagy by the p300acetyltransferase.J Biol Chem,2009,284(10):6322-6328
[36]Madeo F,Eisenberg T,Pietrocola F,et al.Spermidine in health and disease.Science,2018,359(6374):pii eaan2788
[37]Lee I H,Cao L,Mostoslavsky R,et al.A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy.Proc NatlAcad Sci USA.2008,105(9):3374-3379
[38]杨莉,肖凌,陈临溪.自噬与肺部疾病研究进展.生物化学与生物物理进展,2012,39(9):861-868Yang L,Xiao L,Chen L X.Prog Biochem Biophys,2012,39(9):861-868
[39]林芳,顾振纶,秦正红.自噬及其在细胞代谢和疾病中的作用.生物化学与生物物理,2005,32(4):298-303Lin F,Gu Z L,Qin Z H.Prog Biochem Biophys,2005,32(4):298-303
[40]谢凤,柳威,陈临溪.自噬参与心脏疾病调控的研究进展.生物化学与生物物理进展,2012,39(3):224-233Xie F,Liu W,Chen L X.Prog Biochem Biophys,2012,39(3):224-233