胱天蛋白酶3

胱天蛋白酶3
已知的結構 PDB 直系同源搜索: PDBe RCSB PDBID列表 1CP3、​1GFW、​1I3O、​1NME、​1NMQ、​1NMS、​1PAU、​1QX3、​1RE1、​1RHJ、​1RHK、​1RHM、​1RHQ、​1RHR、​1RHU、​2C1E、​2C2K、​2C2M、​2C2O、​2CDR、​2CJX、​2CJY、​2CNK、​2CNL、​2CNN、​2CNO、​2DKO、​2H5I、​2H5J、​2H65、​2J30、​2J31、​2J32、​2J33、​2XYG、​2XYH、​2XYP、​2XZD、​2XZT、​2Y0B、​3DEH、​3DEI、​3DEJ、​3DEK、​3EDQ、​3GJQ、​3GJR、​3GJS、​3GJT、​3H0E、​3ITN、​3KJF、​3PCX、​3PD0、​3PD1、​4DCJ、​4DCO、​4DCP、​4EHA、​4EHD、​4EHF、​4EHH、​4EHK、​4EHL、​4EHN、​4JJE、​4JQY、​4JQZ、​4JR0、​4PRY、​4PS0、​4QTX、​4QTY、​4QU0、​4QU5、​4QU8、​4QU9、​4QUA、​4QUB、​4QUD、​4QUE、​4QUG、​4QUH、​4QUI、​4QUJ、​4QUL、​5IC4
識別號
别名	CASP3；, CPP32, CPP32B, SCA-1, caspase 3
外部ID	OMIM：600636 MGI：107739 HomoloGene：37912 GeneCards：CASP3
為以下藥物的標靶
emricasan[1]
基因位置（小鼠） 染色体 小鼠8号染色体[2] 基因座 8 B1.1|8 26.39 cM 起始 47,070,326 bp[2] 终止 47,092,724 bp[2]
RNA表达模式
查阅更多表达数据
基因本體 分子功能 • 半胱氨酸型肽酶活性 • 肽酶活性 • 血浆蛋白结合 • phospholipase A2 activator activity • cyclin-dependent protein serine/threonine kinase inhibitor activity • cysteine-type endopeptidase activity involved in apoptotic process • cysteine-type endopeptidase activity involved in execution phase of apoptosis • cysteine-type endopeptidase activity • 水解酶活性 • cysteine-type endopeptidase activator activity involved in apoptotic process • aspartic-type endopeptidase activity • 蛋白酶結合 • death receptor binding • 大分子复合物结合 • cysteine-type endopeptidase activity involved in apoptotic signaling pathway 細胞組分 • 細胞質 • 细胞质基质 • 核质 • 死亡誘導信號復合體 • 脂筏模型 • 细胞核 • soma 生物學過程 • cellular response to organic substance • neuron apoptotic process • cell fate commitment • response to estradiol • intracellular signal transduction • response to hypoxia • response to amino acid • apoptotic DNA fragmentation • response to organic cyclic compound • negative regulation of cyclin-dependent protein serine/threonine kinase activity • response to antibiotic • platelet formation • protein processing • response to nicotine • response to metal ion • negative regulation of cell cycle • 傷口癒合 • response to glucocorticoid • cellular response to organic cyclic compound • B cell homeostasis • negative regulation of apoptotic process • 听觉 • response to glucose • response to organic substance • hippo signaling • glial cell apoptotic process • keratinocyte differentiation • 蛋白酶解 • cellular response to DNA damage stimulus • T cell homeostasis • response to tumor necrosis factor • negative regulation of activated T cell proliferation • 心脏发育 • response to lipopolysaccharide • positive regulation of neuron apoptotic process • response to wounding • neuron differentiation • extrinsic apoptotic signaling pathway in absence of ligand • 学习和记忆 • positive regulation of apoptotic process • erythrocyte differentiation • apoptotic signaling pathway • negative regulation of B cell proliferation • response to cobalt ion • hippocampus development • response to UV • response to X-ray • response to hydrogen peroxide • regulation of macroautophagy • neurotrophin TRK receptor signaling pathway • execution phase of apoptosis • intrinsic apoptotic signaling pathway in response to osmotic stress • cellular response to staurosporine • 细胞凋亡 • cytokine-mediated signaling pathway • activation of cysteine-type endopeptidase activity involved in apoptotic process • positive regulation of catalytic activity • 黄体溶解 • axonal fasciculation • striated muscle cell differentiation • leukocyte apoptotic process • regulation of protein stability • positive regulation of amyloid-beta formation • anterior neural tube closure Sources:Amigo / QuickGO
直系同源
物種	人類	小鼠
Entrez	836	12367
Ensembl	ENSG00000164305	ENSMUSG00000031628
UniProt	P42574	P70677
mRNA​序列	​NM_004346 ​NM_032991	NM_009810 ​NM_001284409
蛋白序列	NP_004337 ​NP_116786 ​NP_001341706 ​NP_001341708 ​NP_001341709 ​NP_001341710 ​NP_001341711 ​NP_001341712 ​NP_001341713	NP_001271338 ​NP_033940
基因位置​（UCSC）	无数据	Chr 8: 47.07 – 47.09 Mb
PubMed​查找	[3]	[4]
維基數據
檢視/編輯人類 檢視/編輯小鼠

胱天蛋白酶3（英语：Caspase 3）是一种在人类中由CASP3基因编码的酶。该酶能与胱天蛋白酶8和胱天蛋白酶9产生相互作用。许多可获得完整基因组数据的哺乳动物都已鉴定出CASP3直系同源物。[5]鸟类、蜥蜴、滑体动物和真骨类中也存在独特的直系同源物。

胱天蛋白酶3是胱天蛋白酶（Caspase）家族的成员。[6]胱天蛋白酶的连续激活在细胞凋亡的执行阶段发挥着核心作用。胱天蛋白酶以无活性的酶原形式存在，在保守的天冬氨酸残基处经历蛋白水解加工，产生一大一小两个亚基，然后二聚化形成活性酶。该蛋白酶可裂解并激活胱天蛋白酶6和7，其本身则由胱天蛋白酶8、9和10加工和激活。该蛋白酶是参与裂解前类淀粉蛋白质的主要胱天蛋白酶，而前类淀粉蛋白质与阿茲海默症中的神经元死亡有关。[7]该基因的选择性剪接会产生编码相同蛋白质的两个转录变体。[8]

TNF-R1信号通路。灰色虚线代表多个步骤

导致胱天蛋白酶3激活的途径[9]

胱天蛋白酶3具有许多目前已知的胱天蛋白酶共有的典型特征。例如，其活性位点包含半胱氨酸残基（Cys-163）和组氨酸残基（His-121），当它位于特定的4个氨基酸序列中时，它能够稳定蛋白质序列肽键裂解到天冬氨酸的羧基末端侧。[10][11]这种特异性使得胱天蛋白酶具有有极高的选择性，对天冬氨酸的偏好是谷氨酸的2万倍。[12]胱天蛋白酶在细胞中的一个关键特征是它们以未活化的前酶形式存在，称为胱天蛋白酶原，直到生化变化引起它们的激活为止。每个胱天蛋白酶原都有一个约20kDa的N端大亚基，后面跟着一个约10kDa的小亚基，分别称为p20和p10。[13]

底物特异性

正常情况下，胱天蛋白酶识别其底物上的四肽序列并水解天冬氨酸残基后的肽键。胱天蛋白酶3和7通过识别四肽基序Asp-x-x-Asp共享类似的底物特异性。[14]C端天冬氨酸是绝对必需的，而其他三个位置的变化是可以容忍的。[15]胱天蛋白酶底物特异性已广泛应用于基于胱天蛋白酶的抑制剂和药物设计。[16]

结构

胱天蛋白酶3的p12（粉色）和 p17（浅蓝色）亚基，其β折叠结构分别为红色和蓝色；在Pymol中从1rhm.pdb生成的图像

胱天蛋白酶3（也称为CPP32、Yama或apopain）[17][18][19]是由一个32kDa的酶原形成，该酶原被切割成17kDa和12kDa亚基。当胱天蛋白酶原在特定残基处裂解时，活性异四聚体就能通过疏水相互作用形成，导致来自p17的四个反平行β折叠和来自p12的两个反平行β折叠结合在一起形成异二聚体，该异二聚体又与另一个异二聚体相互作用形成完整的由α螺旋包围的12链β折叠结构，这是胱天蛋白酶特有的。[13][20]当异二聚体头尾相连时，分子两端各有一个由两个参与亚基的残基形成的活性位点，尽管必要的Cys-163和His-121残基位于p17（较大的）亚基上。[20]

机制

胱天蛋白酶3活性位点的Cys-285（黄色）和His-237（绿色和深蓝色），p12亚基为粉色，p17亚基为浅蓝色；在Pymol中从1rhm.pdb生成的图像

胱天蛋白酶3的催化位点涉及Cys-163的硫醇基团和His-121的咪唑环。His-121稳定关键天冬氨酸残基的羰基，而Cys-163则攻击最终裂解肽键。Cys-163和Gly-238还可以通过氢键稳定底物-酶复合物的四面体过渡态。[20]在体外，已发现胱天蛋白酶3更喜欢肽序列 DEVDG（Asp-Glu-Val-Asp-Gly），其切割发生在第二个天冬氨酸残基的羧基侧（D和G之间）。[12][20][21]胱天蛋白酶3在较宽的pH范围内具有活性，该范围比许多其他执行型胱天蛋白酶稍高（碱性更强）。这一广泛的范围表明胱天蛋白酶3在正常和凋亡细胞条件下都可以完全活跃。[22]

激活

胱天蛋白酶3在凋亡细胞中通过外在（死亡配体）和内在（线粒体）途径被激活。[13][23]胱天蛋白酶3的酶原特征是必要的，因为如果不受调节，胱天蛋白酶的活性会不加区别地杀死细胞。[24]作为执行型胱天蛋白酶，胱天蛋白酶3酶原实际上没有活性，直到凋亡信号事件发生后被启动型胱天蛋白酶切割。[25]此类信号事件之一是将颗粒酶B引入杀伤性T细胞针对凋亡的细胞中，该颗粒酶B可以激活启动型胱天蛋白酶。[26][27]这种外在激活随后触发细胞凋亡途径的标志性胱天蛋白酶级联特征，其中胱天蛋白酶3发挥主导作用。[11]在内在激活过程中，来自线粒体的细胞色素c与胱天蛋白酶9、凋亡激活因子1（Apaf-1）和ATP结合作用来处理胱天蛋白酶3酶原。[21][27][28]这些分子足以在体外激活胱天蛋白酶3，但体内还需要其他调节蛋白。[28]山竹（Garcinia mangostana）提取物已被证明可以抑制β淀粉样蛋白处理的人类神经元细胞中胱天蛋白酶3的激活。[29]

抑制

抑制胱天蛋白酶的一种方法是通过IAP（凋亡抑制剂）蛋白家族，其中包括c-IAP1、c-IAP2、XIAP和ML-IAP。[20]XIAP结合并抑制启动型胱天蛋白酶9，后者直接参与执行型胱天蛋白酶3的激活。[28]然而，在胱天蛋白酶级联过程中，胱天蛋白酶3通过在特定位点切割胱天蛋白酶9来抑制XIAP的活性，从而阻止XIAP结合来抑制胱天蛋白酶9的活性。[30]

相互作用

胱天蛋白酶3已被证明可以与以下物质相互作用：

• 胱天蛋白酶8（CASP8）[31][32]
• NMT2[33]
• CFLAR[34][35]
• DCC[36]
• GroEL[37][38]
• HCLS1[39][40]
• Survivin[41][42]
• TRAF3[43][44]
• XIAP[45][46][47][48][49][50]
• NFE2L2[51]

生物学功能

人们发现胱天蛋白酶3对于正常的大脑发育是必需的，它在细胞凋亡中也发挥着典型作用，负责染色质浓缩和DNA碎裂。[21]血液中胱天蛋白酶3片段（p17）水平升高是近期心肌梗死的征兆。[52]现在的研究表明，胱天蛋白酶3可能在胚胎和造血干细胞分化中发挥作用。[53]

参见

• 蛋白酶解图谱（英语：The Proteolysis Map）
• 胱天蛋白酶
• 半胱天冬酶原活化物1（PAC-1）

参考文献

1. 對Caspase 3起作用的藥物；在維基數據上查看/編輯參考. 
2. GRCm38: Ensembl release 89: ENSMUSG00000031628 - Ensembl, May 2017
3. Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
4. Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
5. OrthoMaM phylogenetic marker: CASP3 coding sequence. [2009-12-20]. （原始内容存档于2016-03-03）. 
6. Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J. Human ICE/CED-3 protease nomenclature. Cell. October 1996, 87 (2): 171. PMID 8861900. S2CID 5345060. doi:10.1016/S0092-8674(00)81334-3 . 
7. Gervais FG, Xu D, Robertson GS, Vaillancourt JP, Zhu Y, Huang J, LeBlanc A, Smith D, Rigby M, Shearman MS, Clarke EE, Zheng H, Van Der Ploeg LH, Ruffolo SC, Thornberry NA, Xanthoudakis S, Zamboni RJ, Roy S, Nicholson DW. Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-beta precursor protein and amyloidogenic A beta peptide formation. Cell. April 1999, 97 (3): 395–406. PMID 10319819. S2CID 17524567. doi:10.1016/s0092-8674(00)80748-5 . 
8. Entrez Gene: CASP3 caspase 3, apoptosis-related cysteine peptidase. 
9. Harrington HA, Ho KL, Ghosh S, Tung KC. Construction and analysis of a modular model of caspase activation in apoptosis. Theoretical Biology & Medical Modelling. 2008, 5 (1): 26. PMC 2672941 . PMID 19077196. doi:10.1186/1742-4682-5-26 . 
10. Wyllie AH. Apoptosis: an overview. British Medical Bulletin. 1997, 53 (3): 451–65. PMID 9374030. doi:10.1093/oxfordjournals.bmb.a011623 . 
11. Perry DK, Smyth MJ, Stennicke HR, Salvesen GS, Duriez P, Poirier GG, Hannun YA. Zinc is a potent inhibitor of the apoptotic protease, caspase-3. A novel target for zinc in the inhibition of apoptosis. The Journal of Biological Chemistry. July 1997, 272 (30): 18530–3. PMID 9228015. doi:10.1074/jbc.272.30.18530 . 
12. Stennicke HR, Renatus M, Meldal M, Salvesen GS. Internally quenched fluorescent peptide substrates disclose the subsite preferences of human caspases 1, 3, 6, 7 and 8. The Biochemical Journal. September 2000, 350 (2): 563–8. PMC 1221285 . PMID 10947972. doi:10.1042/0264-6021:3500563. 
13. Salvesen GS. Caspases: opening the boxes and interpreting the arrows. Cell Death and Differentiation. January 2002, 9 (1): 3–5. PMID 11803369. S2CID 31274387. doi:10.1038/sj.cdd.4400963. 
14. Agniswamy J, Fang B, Weber IT. Plasticity of S2-S4 specificity pockets of executioner caspase-7 revealed by structural and kinetic analysis. The FEBS Journal. September 2007, 274 (18): 4752–65. PMID 17697120. S2CID 1860924. doi:10.1111/j.1742-4658.2007.05994.x. 
15. Fang B, Boross PI, Tozser J, Weber IT. Structural and kinetic analysis of caspase-3 reveals role for s5 binding site in substrate recognition. Journal of Molecular Biology. July 2006, 360 (3): 654–66. PMID 16781734. doi:10.1016/j.jmb.2006.05.041. 
16. Weber IT, Fang B, Agniswamy J. Caspases: structure-guided design of drugs to control cell death. Mini Reviews in Medicinal Chemistry. October 2008, 8 (11): 1154–62. PMID 18855730. doi:10.2174/138955708785909899. 
17. Fernandes-Alnemri T, Litwack G, Alnemri ES. CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. The Journal of Biological Chemistry. December 1994, 269 (49): 30761–4. PMID 7983002. doi:10.1016/S0021-9258(18)47344-9 . 
18. Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS, Dixit VM. Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell. June 1995, 81 (5): 801–9. PMID 7774019. S2CID 18866447. doi:10.1016/0092-8674(95)90541-3 . 
19. Nicholson DW, Ali A, Thornberry NA, Vaillancourt JP, Ding CK, Gallant M, Gareau Y, Griffin PR, Labelle M, Lazebnik YA. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature. July 1995, 376 (6535): 37–43. Bibcode:1995Natur.376...37N. PMID 7596430. S2CID 4240789. doi:10.1038/376037a0. 
20. Lavrik IN, Golks A, Krammer PH. Caspases: pharmacological manipulation of cell death. The Journal of Clinical Investigation. October 2005, 115 (10): 2665–72. PMC 1236692 . PMID 16200200. doi:10.1172/JCI26252. 
21. Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death and Differentiation. February 1999, 6 (2): 99–104. PMID 10200555. doi:10.1038/sj.cdd.4400476 . 
22. Stennicke HR, Salvesen GS. Biochemical characteristics of caspases-3, -6, -7, and -8. The Journal of Biological Chemistry. October 1997, 272 (41): 25719–23. PMID 9325297. doi:10.1074/jbc.272.41.25719 . 
23. Ghavami S, Hashemi M, Ande SR, Yeganeh B, Xiao W, Eshraghi M, Bus CJ, Kadkhoda K, Wiechec E, Halayko AJ, Los M. Apoptosis and cancer: mutations within caspase genes. Journal of Medical Genetics. August 2009, 46 (8): 497–510. PMID 19505876. doi:10.1136/jmg.2009.066944 . 
24. Boatright KM, Salvesen GS. Mechanisms of caspase activation. Current Opinion in Cell Biology. December 2003, 15 (6): 725–31. PMID 14644197. doi:10.1016/j.ceb.2003.10.009. 
25. Walters J, Pop C, Scott FL, Drag M, Swartz P, Mattos C, Salvesen GS, Clark AC. A constitutively active and uninhibitable caspase-3 zymogen efficiently induces apoptosis. The Biochemical Journal. December 2009, 424 (3): 335–45. PMC 2805924 . PMID 19788411. doi:10.1042/BJ20090825. 
26. Gallaher BW, Hille R, Raile K, Kiess W. Apoptosis: live or die--hard work either way!. Hormone and Metabolic Research. September 2001, 33 (9): 511–9. PMID 11561209. S2CID 36623826. doi:10.1055/s-2001-17213. 
27. Katunuma N, Matsui A, Le QT, Utsumi K, Salvesen G, Ohashi A. Novel procaspase-3 activating cascade mediated by lysoapoptases and its biological significances in apoptosis. Advances in Enzyme Regulation. 2001, 41 (1): 237–50. PMID 11384748. doi:10.1016/S0065-2571(00)00018-2. 
28. Li P, Nijhawan D, Wang X. Mitochondrial activation of apoptosis. Cell. January 2004, 116 (2 Suppl): S57–9, 2 p following S59. PMID 15055583. S2CID 5180966. doi:10.1016/S0092-8674(04)00031-5 . 
29. Moongkarndi P, Srisawat C, Saetun P, Jantaravinid J, Peerapittayamongkol C, Soi-ampornkul R, Junnu S, Sinchaikul S, Chen ST, Charoensilp P, Thongboonkerd V, Neungton N. Protective effect of mangosteen extract against beta-amyloid-induced cytotoxicity, oxidative stress and altered proteome in SK-N-SH cells (PDF). Journal of Proteome Research. May 2010, 9 (5): 2076–86 [2024-01-25]. PMID 20232907. doi:10.1021/pr100049v. （原始内容存档 (PDF)于2023-08-04）. 
30. Denault JB, Eckelman BP, Shin H, Pop C, Salvesen GS. Caspase 3 attenuates XIAP (X-linked inhibitor of apoptosis protein)-mediated inhibition of caspase 9. The Biochemical Journal. July 2007, 405 (1): 11–9. PMC 1925235 . PMID 17437405. doi:10.1042/BJ20070288. 
31. Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES. Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria. The Journal of Biological Chemistry. April 2002, 277 (16): 13430–7. PMID 11832478. doi:10.1074/jbc.M108029200 . 
32. Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES. Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases. Proceedings of the National Academy of Sciences of the United States of America. December 1996, 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. PMC 26159 . PMID 8962078. doi:10.1073/pnas.93.25.14486 . 
33. Selvakumar, P.; Sharma, RK. Role of calpain and caspase system in the regulation of N-myristoyltransferase in human colon cancer (Review).. Int J Mol Med. May 2007, 19 (5): 823–7. PMID 17390089. doi:10.3892/ijmm.19.5.823 . 
34. Shu HB, Halpin DR, Goeddel DV. Casper is a FADD- and caspase-related inducer of apoptosis. Immunity. June 1997, 6 (6): 751–63. PMID 9208847. doi:10.1016/S1074-7613(00)80450-1 . 
35. Han DK, Chaudhary PM, Wright ME, Friedman C, Trask BJ, Riedel RT, Baskin DG, Schwartz SM, Hood L. MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death. Proceedings of the National Academy of Sciences of the United States of America. October 1997, 94 (21): 11333–8. Bibcode:1997PNAS...9411333H. PMC 23459 . PMID 9326610. doi:10.1073/pnas.94.21.11333 . 
36. Forcet C, Ye X, Granger L, Corset V, Shin H, Bredesen DE, Mehlen P. The dependence receptor DCC (deleted in colorectal cancer) defines an alternative mechanism for caspase activation. Proceedings of the National Academy of Sciences of the United States of America. March 2001, 98 (6): 3416–21. Bibcode:2001PNAS...98.3416F. PMC 30668 . PMID 11248093. doi:10.1073/pnas.051378298 . 
37. Samali A, Cai J, Zhivotovsky B, Jones DP, Orrenius S. Presence of a pre-apoptotic complex of pro-caspase-3, Hsp60 and Hsp10 in the mitochondrial fraction of jurkat cells. The EMBO Journal. April 1999, 18 (8): 2040–8. PMC 1171288 . PMID 10205158. doi:10.1093/emboj/18.8.2040. 
38. Xanthoudakis S, Roy S, Rasper D, Hennessey T, Aubin Y, Cassady R, Tawa P, Ruel R, Rosen A, Nicholson DW. Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases during apoptosis. The EMBO Journal. April 1999, 18 (8): 2049–56. PMC 1171289 . PMID 10205159. doi:10.1093/emboj/18.8.2049. 
39. Ruzzene M, Penzo D, Pinna LA. Protein kinase CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) induces apoptosis and caspase-dependent degradation of haematopoietic lineage cell-specific protein 1 (HS1) in Jurkat cells. The Biochemical Journal. May 2002, 364 (Pt 1): 41–7. PMC 1222543 . PMID 11988074. doi:10.1042/bj3640041. 
40. Chen YR, Kori R, John B, Tan TH. Caspase-mediated cleavage of actin-binding and SH3-domain-containing proteins cortactin, HS1, and HIP-55 during apoptosis. Biochemical and Biophysical Research Communications. November 2001, 288 (4): 981–9. PMID 11689006. doi:10.1006/bbrc.2001.5862. 
41. Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, Reed JC. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Research. December 1998, 58 (23): 5315–20. PMID 9850056. 
42. Shin S, Sung BJ, Cho YS, Kim HJ, Ha NC, Hwang JI, Chung CW, Jung YK, Oh BH. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry. January 2001, 40 (4): 1117–23. PMID 11170436. doi:10.1021/bi001603q. 
43. Lee ZH, Lee SE, Kwack K, Yeo W, Lee TH, Bae SS, Suh PG, Kim HH. Caspase-mediated cleavage of TRAF3 in FasL-stimulated Jurkat-T cells. Journal of Leukocyte Biology. March 2001, 69 (3): 490–6. PMID 11261798. S2CID 34256107. doi:10.1189/jlb.69.3.490. 
44. Leo E, Deveraux QL, Buchholtz C, Welsh K, Matsuzawa S, Stennicke HR, Salvesen GS, Reed JC. TRAF1 is a substrate of caspases activated during tumor necrosis factor receptor-alpha-induced apoptosis. The Journal of Biological Chemistry. March 2001, 276 (11): 8087–93. PMID 11098060. doi:10.1074/jbc.M009450200 . 
45. Suzuki Y, Nakabayashi Y, Takahashi R. Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death. Proceedings of the National Academy of Sciences of the United States of America. July 2001, 98 (15): 8662–7. Bibcode:2001PNAS...98.8662S. PMC 37492 . PMID 11447297. doi:10.1073/pnas.161506698 . 
46. Silke J, Hawkins CJ, Ekert PG, Chew J, Day CL, Pakusch M, Verhagen AM, Vaux DL. The anti-apoptotic activity of XIAP is retained upon mutation of both the caspase 3- and caspase 9-interacting sites. The Journal of Cell Biology. April 2002, 157 (1): 115–24. PMC 2173256 . PMID 11927604. doi:10.1083/jcb.200108085. 
47. Riedl SJ, Renatus M, Schwarzenbacher R, Zhou Q, Sun C, Fesik SW, Liddington RC, Salvesen GS. Structural basis for the inhibition of caspase-3 by XIAP. Cell. March 2001, 104 (5): 791–800. PMID 11257232. S2CID 17915093. doi:10.1016/S0092-8674(01)00274-4 . 
48. Roy N, Deveraux QL, Takahashi R, Salvesen GS, Reed JC. The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. The EMBO Journal. December 1997, 16 (23): 6914–25. PMC 1170295 . PMID 9384571. doi:10.1093/emboj/16.23.6914. 
49. Deveraux QL, Takahashi R, Salvesen GS, Reed JC. X-linked IAP is a direct inhibitor of cell-death proteases. Nature. July 1997, 388 (6639): 300–4. Bibcode:1997Natur.388..300D. PMID 9230442. S2CID 4395885. doi:10.1038/40901 . 
50. Suzuki Y, Nakabayashi Y, Nakata K, Reed JC, Takahashi R. X-linked inhibitor of apoptosis protein (XIAP) inhibits caspase-3 and -7 in distinct modes. The Journal of Biological Chemistry. July 2001, 276 (29): 27058–63. PMID 11359776. doi:10.1074/jbc.M102415200 . 
51. Ohtsubo T, Kamada S, Mikami T, Murakami H, Tsujimoto Y. Identification of NRF2, a member of the NF-E2 family of transcription factors, as a substrate for caspase-3(-like) proteases. Cell Death and Differentiation. September 1999, 6 (9): 865–72. PMID 10510468. doi:10.1038/sj.cdd.4400566 . 
52. Agosto M, Azrin M, Singh K, Jaffe AS, Liang BT. Serum caspase-3 p17 fragment is elevated in patients with ST-segment elevation myocardial infarction: a novel observation. Journal of the American College of Cardiology. January 2011, 57 (2): 220–1. PMID 21211695. doi:10.1016/j.jacc.2010.08.628 . 
53. Abdul-Ghani M, Megeney LA. Rehabilitation of a contract killer: caspase-3 directs stem cell differentiation. Cell Stem Cell. June 2008, 2 (6): 515–6. PMID 18522841. doi:10.1016/j.stem.2008.05.013 . 

拓展阅读

• Cohen GM. Caspases: the executioners of apoptosis. The Biochemical Journal. August 1997, 326 (Pt 1): 1–16. PMC 1218630 . PMID 9337844. doi:10.1042/bj3260001. 
• Roig J, Traugh JA. Cytostatic p21 G protein-activated protein kinase gamma-PAK. Vitamins & Hormones 62. 2001: 167–98. ISBN 9780127098623. PMID 11345898. doi:10.1016/S0083-6729(01)62004-1. 
• Zhao LJ, Zhu H. Structure and function of HIV-1 auxiliary regulatory protein Vpr: novel clues to drug design. Current Drug Targets. Immune, Endocrine and Metabolic Disorders. December 2004, 4 (4): 265–75. PMID 15578977. doi:10.2174/1568008043339668. 
• Le Rouzic E, Benichou S. The Vpr protein from HIV-1: distinct roles along the viral life cycle. Retrovirology. 2006, 2 (1): 11. PMC 554975 . PMID 15725353. doi:10.1186/1742-4690-2-11 . 
• Sykes MC, Mowbray AL, Jo H. Reversible glutathiolation of caspase-3 by glutaredoxin as a novel redox signaling mechanism in tumor necrosis factor-alpha-induced cell death. Circulation Research. February 2007, 100 (2): 152–4. PMID 17272816. S2CID 12684325. doi:10.1161/01.RES.0000258171.08020.72. 

外部链接

• 肽酶及其抑制剂的MEROPS在线数据库：C14.003 （页面存档备份，存于互联网档案馆）
• Apoptosis & Caspase 3 （页面存档备份，存于互联网档案馆） - 蛋白酶解图谱（英语：The Proteolysis Map）（动画）