Please wait a minute...

中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2023, Vol. 43 Issue (2/3): 130-140    DOI: 10.13523/j.cb.2208021
综述     
促凋亡蛋白BAK的功能及在病毒感染中作用的研究进展*
徐炜民,邓鑫,伍锐**()
四川农业大学动物医学院 猪病研究中心 成都 610000
Research Progress on the Function of Pro-apoptotic Protein BAK and Its Role in Virus Infection
XU Wei-min,DENG Xin,WU Rui**()
Research Center of Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 610000, China
 全文: PDF(1982 KB)   HTML
摘要：

BAK蛋白从属于BCL-2家族,是细胞凋亡途径中的关键蛋白。BAK蛋白在凋亡信号的刺激下被激活,并在线粒体上集聚成簇后诱导细胞色素c等促凋亡物质释放,通过caspase级联反应放大凋亡信号,最终诱导细胞死亡。目前的BAK研究普遍用于针对癌细胞凋亡逃逸及病毒对机体细胞免疫的逃逸过程,而病毒等病原体与BAK之间的作用机制、影响胞内凋亡和炎症通路的激活以及炎性因子活化的研究较少。因此对BAK蛋白结构、功能和BAK可能介导的相关通路进行介绍,并对其在病毒感染研究中的作用进展进行了分析,以期为促凋亡蛋白BAK在病毒感染中作用的深入研究提供一些理论基础。
关键词： 促凋亡蛋白;  BAK;  细胞凋亡;  BCL蛋白家族;  病毒感染    
Abstract:

BAK protein, a member of the BCL-2 family, is a key protein in the apoptosis pathway. It is activated under the stimulation of apoptotic signals, and after clustering on mitochondria, induces the release of cytochrome c and other pro-apoptotic substances, amplifies apoptosis signals through caspase cascade reaction, and finally promotes cell death. At present, the role of BAK in the apoptosis escape of cancer cells and the activation of intracellular inflammatory response has been confirmed, but the mechanism of action between viruses and other pathogens and BAK, the activation process of intracellular apoptosis and inflammatory pathways are less studied. Therefore, in this paper, the structure and function of BAK protein and the related pathways mediated by BAK are introduced, and the progress of its role in the study of virus infection is analyzed, in order to provide some theoretical basis for the in-depth study of the pro-apoptotic protein BAK in virus infection.
Key words: Pro-apoptotic protein    BAK    Apoptosis    BCL protein family    Viral infection
收稿日期: 2022-08-15 出版日期: 2023-03-31
ZTFLH:  Q946.1  
基金资助: *国家重点研发计划(2021YFD1100206)
通讯作者: **伍锐     E-mail: wurui1977@163.com
服务　　
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章　　
徐炜民
邓鑫
伍锐

引用本文:

徐炜民, 邓鑫, 伍锐. 促凋亡蛋白BAK的功能及在病毒感染中作用的研究进展*[J]. 中国生物工程杂志, 2023, 43(2/3): 130-140.

XU Wei-min, DENG Xin, WU Rui. Research Progress on the Function of Pro-apoptotic Protein BAK and Its Role in Virus Infection. China Biotechnology, 2023, 43(2/3): 130-140.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2208021    或    https://manu60.magtech.com.cn/biotech/CN/Y2023/V43/I2/3/130

图1  BAK 蛋白结构(由PyMol蛋白结构预测软件制作)
图2  BAK蛋白激活形式
图3  BAK的表达调控机制
病毒类型 感染病毒后对BAK的影响
腺病毒(ADV) ADV通过合成自身E1B 19K蛋白,干扰宿主蛋白的合成,且可以特异性集合BAK,抑制其激活和聚集,减少了细胞凋亡和自身免疫情况,以达到扩增自身的目的[57]
发热伴血小板减少综合征病毒
(SFTSV)		 在感染SFTSV宿主后,往往引起全身性炎症,因此产生分支结果。细胞感染病毒后,病毒通过激活BAK蛋白引起细胞死亡且产生炎性因子的状况无法有效治疗,促炎大于抗炎效应,导致机体免疫功能损耗,导致病毒大量增殖;若细胞自身抗炎效应抑制了BAK激活,则会降低细胞的促炎效应,当免疫系统消除病毒后便会恢复健康[59]
塞姆利基森林病毒
(SFV)		 SFV同样是利用胞内BAK诱导细胞凋亡病毒的一员,但研究发现SFV诱导的细胞凋亡主要依赖于BAK而不是BAX,这二者之间的关系也逐渐清晰,且逐步发现激活BAX更倾向于是细胞自身诱导的凋亡,而BAK更容易受到外来病原的利用而引发凋亡,这可能与二者之间的分布有关,BAK激活和聚集性比BAX更快速可能也是诱因之一[60]
水泡性口炎病毒
(VSV)		 VSV感染宿主细胞后会引发强烈的炎症反应,研究发现VSV通过抑制MCL-1和BCL-XL活性,增加BAK活性从而诱导细胞凋亡,且VSV同样更倾向于诱导激活BAK而不是BAX,病毒通过自身蛋白质M的合成激活胞内游离Bid成tBid而引起BAK活化,产生后续炎症反应[61]
乙型脑炎病毒
(JEV)		 JEV感染宿主神经细胞引起的炎症分为两个阶段。第一个阶段较为短暂,是病毒主要合成自身蛋白质的时期,通过将自身蛋白质NS3和NS5组合成熟后进入下一个阶段;将抗凋亡蛋白BCL-XL激活且上调表达从而抑制BAK,使细胞凋亡程度下降,导致病毒复制量增加,病毒载量提升,最后进入机体引发病毒血症[62]
表1  BAK在病毒感染中的研究
[1] Willis S N, Fletcher J I, Kaufmann T, et al. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science, 2007, 315(5813): 856-859.
doi: 10.1126/science.1133289 pmid: 17289999
[2] Brooks C, Wei Q Q, Feng L P, et al. Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(28): 11649-11654.
[3] Vince J E, De Nardo D, Gao W Q, et al. The mitochondrial apoptotic effectors BAX/BAK activate caspase-3 and-7 to trigger NLRP 3 inflammasome and caspase-8 driven IL-1β activation. Cell Reports, 2018, 25(9): 2339-2353.e4.
doi: 10.1016/j.celrep.2018.10.103
[4] Edlich F. BCL-2 proteins and apoptosis: recent insights and unknowns. Biochemical and Biophysical Research Communications, 2018, 500(1): 26-34.
doi: S0006-291X(17)31321-9 pmid: 28676391
[5] Pogmore J P, Uehling D, Andrews D W. Pharmacological targeting of executioner proteins: controlling life and death. Journal of Medicinal Chemistry, 2021, 64(9): 5276-5290.
doi: 10.1021/acs.jmedchem.0c02200 pmid: 33939407
[6] Glab J A, Cao Z P, Puthalakath H. Bcl-2 family proteins, beyond the veil. International Review of Cell and Molecular Biology, 2020, 351: 1-22.
doi: S1937-6448(19)30120-0 pmid: 32247577
[7] Huang K, O’Neill K L, Li J, et al. BH3-only proteins target BCL-xL/MCL-1, not BAX/BAK, to initiate apoptosis. Cell Research, 2019, 29(11): 942-952.
doi: 10.1038/s41422-019-0231-y pmid: 31551537
[8] Adams J M. BAX and BAK become killers without a BH3 trigger. Cell Research, 2019, 29(12): 967-968.
doi: 10.1038/s41422-019-0253-5 pmid: 31729467
[9] Heimer S, Knoll G, Schulze-Osthoff K, et al. Raptinal bypasses BAX, BAK, and BOK for mitochondrial outer membrane permeabilization and intrinsic apoptosis. Cell Death & Disease, 2019, 10: 556.
[10] Hockings C, Alsop A E, Fennell S C, et al. Mcl-1 and Bcl-xL sequestration of Bak confers differential resistance to BH3-only proteins. Cell Death & Differentiation, 2018, 25(4): 721-734.
[11] Huska J D, Lamb H M, Hardwick J M. Overview of BCL-2 family proteins and therapeutic potentials. Methods in Molecular Biology (Clifton, N J), 2019, 1877: 1-21.
[12] Luo X, O’Neill K L, Huang K. The third model of Bax/Bak activation: a Bcl-2 family feud finally resolved? F1000Res, 2020, 9: 935.
doi: 10.12688/f1000research
[13] Peña-Blanco A, García-Sáez A J. Bax, bak and beyond - mitochondrial performance in apoptosis. The FEBS Journal, 2018, 285(3): 416-431.
doi: 10.1111/febs.2018.285.issue-3
[14] Voss A K, Strasser A. The essentials of developmental apoptosis. F1000Res, 2020, 9: 148.
doi: 10.12688/f1000research
[15] Iyer S, Uren R T, Dengler M A, et al. Robust autoactivation for apoptosis by BAK but not BAX highlights BAK as an important therapeutic target. Cell Death & Disease, 2020, 11: 268.
[16] de Torre-Minguela C, Gómez A I, Couillin I, et al. Gasdermins mediate cellular release of mitochondrial DNA during pyroptosis and apoptosis. FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology, 2021, 35(8): e21757.
[17] Zhang Y, Iqbal S, O’Leary M F N, et al. Altered mitochondrial morphology and defective protein import reveal novel roles for Bax and/or Bak in skeletal muscle. American Journal of Physiology Cell Physiology, 2013, 305(5): C502-C511.
doi: 10.1152/ajpcell.00058.2013
[18] Hu L, Chen M, Chen X R, et al. Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate. Cell Death & Disease, 2020, 11: 281.
[19] Flores-Romero H, Ros U, Garcia-Saez A J. Pore formation in regulated cell death. The EMBO Journal, 2020, 39(23): e105753.
[20] Wei M C, Zong W X, Cheng E H, et al. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science, 2001, 292(5517): 727-730.
doi: 10.1126/science.1059108 pmid: 11326099
[21] Moldoveanu T, Czabotar P E. BAX, BAK, and BOK: a coming of age for the BCL-2 family effector proteins. Cold Spring Harbor Perspectives in Biology, 2020, 12(4): a036319.
doi: 10.1101/cshperspect.a036319
[22] Singh G, Moldoveanu T. Methods to probe conformational activation and mitochondrial activity of proapoptotic BAK. Methods in Molecular Biology. New York: Springer New York, 2018: 185-200.
[23] Iyer S, Uren R T, Kluck R M. Probing BAK and BAX activation and pore assembly with cytochrome c release, limited proteolysis, and oxidant-induced linkage. Methods in Molecular Biology (Clifton, N J), 2019, 1877: 201-216.
[24] Galluzzi L, Vanpouille-Box C. BAX and BAK at the gates of innate immunity. Trends in Cell Biology, 2018, 28(5): 343-345.
doi: S0962-8924(18)30034-5 pmid: 29555208
[25] Li M X, Tan I K L, Ma S B, et al. BAK α6 permits activation by BH3-only proteins and homooligomerization via the canonical hydrophobic groove. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(29): 7629-7634.
[26] Westphal D, Dewson G, Czabotar P E, et al. Molecular biology of Bax and Bak activation and action. Biochimica et Biophysica Acta, 2011, 1813(4): 521-531.
doi: 10.1016/j.bbamcr.2010.12.019 pmid: 21195116
[27] Ye K Q, Meng W X, Sun H B, et al. Characterization of an alternative BAK-binding site for BH3 peptides. Nature Communications, 2020, 11: 3301.
doi: 10.1038/s41467-020-17074-y pmid: 32620849
[28] McArthur K, Whitehead L W, Heddleston J M, et al. BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science, 2018, 359(6378): eaao6047.
doi: 10.1126/science.aao6047
[29] Vila-Julià G, Granadino-Roldán J M, Perez J J, et al. Molecular determinants for the activation/inhibition of Bak protein by BH 3 peptides. Journal of Chemical Information and Modeling, 2020, 60(3): 1632-1643.
doi: 10.1021/acs.jcim.9b01047 pmid: 31944696
[30] Dewson G, Kluck R M. Mechanisms by which Bak and Bax permeabilise mitochondria during apoptosis. Journal of Cell Science, 2009, 122(Pt 16): 2801-2808.
doi: 10.1242/jcs.038166 pmid: 19795525
[31] Dewson G, Kratina T, Sim H W, et al. To trigger apoptosis, Bak exposes its BH 3 domain and homodimerizes via BH3: groove interactions. Molecular Cell, 2008, 30(3): 369-380.
doi: 10.1016/j.molcel.2008.04.005 pmid: 18471982
[32] Mandal T, Shin S, Aluvila S, et al. Assembly of Bak homodimers into higher order homooligomers in the mitochondrial apoptotic pore. Scientific Reports, 2016, 6: 30763.
doi: 10.1038/srep30763 pmid: 27488021
[33] Li K M, van Delft M F, Dewson G. Too much death can kill You: inhibiting intrinsic apoptosis to treat disease. The EMBO Journal, 2021, 40(14): e107341.
[34] Surman D R, Xu Y, Lee M J, et al. Therapeutic synergy in esophageal cancer and mesothelioma is predicted by dynamic BH3 profiling. Molecular Cancer Therapeutics, 2021, 20(8): 1469-1480.
doi: 10.1158/1535-7163.MCT-20-0887 pmid: 34088830
[35] Tran V H, Bartolo R, Westphal D, et al. Bak apoptotic function is not directly regulated by phosphorylation. Cell Death & Disease, 2013, 4(1): e452.
[36] Uren R T, Iyer S, Kluck R M. Pore formation by dimeric Bak and Bax: an unusual pore? Philosophical Transactions of the Royal Society of London Series B, Biological Sciences, 2017, 372(1726): 20160218.
[37] Birkinshaw R W, Iyer S, Lio D, et al. Structure of detergent-activated BAK dimers derived from the inert monomer. Molecular Cell, 2021, 81(10): 2123-2134.e5.
doi: 10.1016/j.molcel.2021.03.014 pmid: 33794146
[38] Cuconati A, Degenhardt K, Sundararajan R, et al. Bak and Bax function to limit adenovirus replication through apoptosis induction. Journal of Virology, 2002, 76(9): 4547-4558.
pmid: 11932420
[39] Pérez-Treviño P, Velásquez M, García N. Mechanisms of mitochondrial DNA escape and its relationship with different metabolic diseases. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2020, 1866(6): 165761.
[40] Lee E F, Grabow S, Chappaz S, et al. Physiological restraint of Bak by Bcl-xL is essential for cell survival. Genes & Development, 2016, 30(10): 1240-1250.
doi: 10.1101/gad.279414.116
[41] Korsmeyer S J, Wei M C, Saito M, et al. Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c. Cell Death & Differentiation, 2000, 7(12): 1166-1173.
[42] Sandow J J, Tan I K, Huang A S, et al. Dynamic reconfiguration of pro-apoptotic BAK on membranes. The EMBO Journal, 2021, 40(20): e107237.
[43] Yeganeh B, Ghavami S, Rahim M N, et al. Autophagy activation is required for influenza A virus-induced apoptosis and replication. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 2018, 1865(2): 364-378.
doi: 10.1016/j.bbamcr.2017.10.014
[44] Lin L, Zhang M, Stoilov P, et al. Developmental attenuation of neuronal apoptosis by neural-specific splicing of Bak1 microexon. Neuron, 2020, 107(6): 1180-1196.e8.
doi: S0896-6273(20)30490-6 pmid: 32710818
[45] Imao T, Nagata S. Apaf-1- and caspase-8-independent apoptosis. Cell Death and Differentiation, 2013, 20(2): 343-352.
doi: 10.1038/cdd.2012.149 pmid: 23197294
[46] Huang K, Zhang J J, O’Neill K L, et al. Cleavage by caspase 8 and mitochondrial membrane association activate the BH3-only protein bid during TRAIL-induced apoptosis. Journal of Biological Chemistry, 2016, 291(22): 11843-11851.
doi: 10.1074/jbc.M115.711051 pmid: 27053107
[47] Simpson D S, Pang J Y, Weir A, et al. Interferon-γ primes macrophages for pathogen ligand-induced killing via a caspase-8 and mitochondrial cell death pathway. Immunity, 2022, 55(3): 423-441.e9.
doi: 10.1016/j.immuni.2022.01.003 pmid: 35139355
[48] Chen W T, Hsu F T, Liu Y C, et al. Fluoxetine induces apoptosis through extrinsic/intrinsic pathways and inhibits ERK/NF-κB-modulated anti-apoptotic and invasive potential in hepatocellular carcinoma cells in vitro. International Journal of Molecular Sciences, 2019, 20(3): 757.
doi: 10.3390/ijms20030757
[49] Galluzzi L, Morselli E, Kepp O, et al. Targeting p53 to mitochondria for cancer therapy. Cell Cycle, 2008, 7(13): 1949-1955.
pmid: 18642442
[50] Nieminen A I, Eskelinen V M, Haikala H M, et al. Myc-induced AMPK-phospho p53 pathway activates Bak to sensitize mitochondrial apoptosis. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(20): E 1839-E1848.
[51] Zhang J, Huang K, O’Neill K L, et al. Bax/Bak activation in the absence of Bid, Bim, Puma, and p53. Cell Death & Disease, 2016, 7(6): e2266.
[52] Degenhardt K, Chen G H, Lindsten T, et al. BAX and BAK mediate p53-independent suppression of tumorigenesis. Cancer Cell, 2002, 2(3): 193-203.
pmid: 12242152
[53] Wang J J, Guo W H, Zhou H, et al. Mitochondrial p53 phosphorylation induces Bak-mediated and caspase-independent cell death. Oncotarget, 2015, 6(19): 17192-17205.
pmid: 25980443
[54] Leu JI-Ju, George D L. Hepatic IGFBP1 is a prosurvival factor that binds to BAK, protects the liver from apoptosis, and antagonizes the proapoptotic actions of p53 at mitochondria. Genes & Development, 2007, 21(23): 3095-3109.
doi: 10.1101/gad.1567107
[55] Chin H S, Li M X, Tan I K L, et al. VDAC2 enables BAX to mediate apoptosis and limit tumor development. Nature Communications, 2018, 9: 4976.
doi: 10.1038/s41467-018-07309-4 pmid: 30478310
[56] Dudko H V, Urban V A, Davidovskii A I, et al. Structure-based modeling of turnover of Bcl-2 family proteins bound to voltage-dependent anion channel 2 (VDAC2): implications for the mechanisms of proapoptotic activation of Bak and Bax in vivo. Computational Biology and Chemistry, 2020, 85: 107203.
doi: 10.1016/j.compbiolchem.2020.107203
[57] Sundararajan R, Cuconati A, Nelson D, et al. Tumor necrosis factor-alpha induces Bax-Bak interaction and apoptosis, which is inhibited by adenovirus E1B 19K. The Journal of Biological Chemistry, 2001, 276(48): 45120-45127.
doi: 10.1074/jbc.M106386200
[58] Cheng Y, Sun F, Wang L, et al. Virus-induced p38 MAPK activation facilitates viral infection. Theranostics, 2020, 10(26): 12223-12240.
doi: 10.7150/thno.50992 pmid: 33204339
[59] Li S F, Li H, Zhang Y L, et al. SFTSV infection induces BAK/BAX-dependent mitochondrial DNA release to trigger NLRP 3 inflammasome activation. Cell Reports, 2020, 30(13): 4370-4385.
doi: 10.1016/j.celrep.2020.02.105
[60] Urban C, Rhême C, Maerz S, et al. Apoptosis induced by Semliki Forest virus is RNA replication dependent and mediated via Bak. Cell Death & Differentiation, 2008, 15(9): 1396-1407.
[61] Zhong Y X, Liao Y, Fang S G, et al. Up-regulation of Mcl-1 and Bak by coronavirus infection of human, avian and animal cells modulates apoptosis and viral replication. PLoS One, 2012, 7(1): e30191.
doi: 10.1371/journal.pone.0030191
[62] Suzuki T, Okamoto T, Katoh H, et al. Infection with flaviviruses requires BCLXL for cell survival. PLoS Pathogens, 2018, 14(9): e1007299.
doi: 10.1371/journal.ppat.1007299
[63] Pearce A F, Lyles D S. Vesicular stomatitis virus induces apoptosis primarily through Bak rather than Bax by inactivating Mcl-1 and Bcl-XL. Journal of Virology, 2009, 83(18): 9102-9112.
doi: 10.1128/JVI.00436-09 pmid: 19587033
[64] Cosentino K, Hertlein V, Jenner A, et al. The interplay between BAX and BAK tunes apoptotic pore growth to control mitochondrial-DNA-mediated inflammation. Molecular Cell, 2022, 82(5): 933-949.e9.
doi: 10.1016/j.molcel.2022.01.008 pmid: 35120587
[1] 王婷,刘凯,李柯颖,陈旭,任广明,杨晓明. 敲除Usp13促进棕榈酸诱导的小鼠肝实质细胞凋亡*[J]. 中国生物工程杂志, 2022, 42(4): 9-16.
[2] 王伟东,杜加茹,张运尚,樊剑鸣. CRISPR/Cas9在人病毒感染相关疾病治疗研究中的应用*[J]. 中国生物工程杂志, 2020, 40(12): 18-24.
[3] 朱永朝,陶金,任萌萌,熊燃,何亚琴,周瑜,卢震辉,杜勇,杨芝红. 自噬抑制肿瘤坏死因子α诱导人胎盘胎儿来源间充质干细胞发生凋亡 *[J]. 中国生物工程杂志, 2019, 39(9): 62-67.
[4] 刘叶,潘玥,郑魏,胡晶. miR-186-5p在酒精诱导的心肌细胞中高表达并通过靶基因XIAP调控细胞凋亡水平 *[J]. 中国生物工程杂志, 2019, 39(5): 53-62.
[5] 代立婷, 吴忠南, 黄翔, 杨杰, 曾慧兰, 王国才, 蒋建伟. 卤地菊乙醇提取物W40单体诱导GLC-82细胞凋亡的分子机制研究[J]. 中国生物工程杂志, 2017, 37(8): 1-7.
[6] 徐安健, 李艳萌, 李斯文, 乌姗娜, 张蓓, 黄坚. PHP14沉默对肺癌细胞凋亡的影响及其机制[J]. 中国生物工程杂志, 2017, 37(7): 12-17.
[7] 白欣艳, 温丽敏, 王玉晶, 王海龙, 解军, 郭睿. ANKRD49通过上调Bcl-xL的表达抑制UV诱导GC-1细胞的凋亡[J]. 中国生物工程杂志, 2017, 37(4): 40-47.
[8] 王小莉, 余庆, 袁雅红, 腾智平, 李东升, 曾毅. 打靶恒河猴CD4+ T细胞的TRIM5α基因影响其感染HIV的能力[J]. 中国生物工程杂志, 2017, 37(2): 15-19.
[9] 万春红, 张志, 李圣纳, 彭以元, 许亮国. TRAF7的研究进展[J]. 中国生物工程杂志, 2016, 36(3): 93-101.
[10] 陈娜子, 姜潮, 李校堃. 内质网应激与疾病[J]. 中国生物工程杂志, 2016, 36(1): 76-85.
[11] 邱华丽, 穰杰, 丁学知, 胡胜标, 张友明, 朱道奇, 夏立秋. 苦瓜MAP30蛋白的原核表达及其生物活性研究[J]. 中国生物工程杂志, 2014, 34(06): 40-46.
[12] 韩笑, 李娜, 杜培革. 抗肿瘤多肽研究进展[J]. 中国生物工程杂志, 2013, 33(6): 93-98.
[13] 张曦, 刘北忠, 高艳军, 黎亮, 高远梅, 胡秀秀, 马鹏鹏, 钟梁. 干扰 GINS2 表达对HL60细胞增殖和凋亡的影响[J]. 中国生物工程杂志, 2013, 33(3): 41-46.
[14] 魏东, 邹浩, 王琳, 王文举, 骆志玲, 张小文. 靶向miRNA干扰Bmi-1诱导胆囊癌细胞凋亡及上调Caspase-3表达的研究[J]. 中国生物工程杂志, 2013, 33(12): 1-8.
[15] 林颖, 李璞, 单敬轩, 陈晓静, 施慧莉, 霍克克. RIOK3促进了caspase-10对PAK2的酶解激活[J]. 中国生物工程杂志, 2012, 32(08): 1-8.
主管：中国科学院 　主办：中国科学院文献情报中心 　中国生物技术发展中心 　中国生物工程学会