Smac模拟物与肿瘤坏死因子α：一种危险的关联？
Smac mimetics and TNFalpha: a dangerous liaison?
作者信息
Wu Hao, Tschopp Jurg, Lin Su-Chang
机构信息
Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA.
出版信息
Cell. 2007 Nov 16;131(4):655-8. doi: 10.1016/j.cell.2007.10.042.
Abstract
Inhibitor of apoptosis proteins (IAPs) such as XIAP, cIAP1, and cIAP2 are upregulated in many cancer cells. It has been thought that small-molecule mimetics of Smac, an endogenous IAP antagonist, might potentiate apoptosis in cancer cells by promoting caspase activation. However, three recent papers, two in Cell (Vince et al., 2007; Varfolomeev et al., 2007) and one in Cancer Cell (Petersen et al., 2007), now report that Smac mimetics primarily kill cancer cells via a different mechanism, the induction of autoubiquitination and degradation of cIAPs, which culminates in TNFalpha-mediated cell death.
摘要
凋亡抑制蛋白（IAPs），如X连锁凋亡抑制蛋白（XIAP）、细胞凋亡抑制蛋白1（cIAP1）和细胞凋亡抑制蛋白2（cIAP2），在许多癌细胞中上调。人们一直认为，内源性IAP拮抗剂Smac的小分子模拟物可能通过促进半胱天冬酶激活来增强癌细胞的凋亡。然而，最近有三篇论文，两篇发表在《细胞》杂志上（文斯等人，2007年；瓦尔福洛梅耶夫等人，2007年），一篇发表在《癌细胞》杂志上（彼得森等人，2007年），现在报道Smac模拟物主要通过一种不同的机制杀死癌细胞，即诱导cIAPs的自身泛素化和降解，最终导致肿瘤坏死因子α（TNFα）介导的细胞死亡。
相似文献
1
Smac mimetics and TNFalpha: a dangerous liaison?Smac模拟物与肿瘤坏死因子α：一种危险的关联？
Cell. 2007 Nov 16;131(4):655-8. doi: 10.1016/j.cell.2007.10.042.
2
Molecular determinants of Smac mimetic induced degradation of cIAP1 and cIAP2.Smac 模拟物诱导 cIAP1 和 cIAP2 降解的分子决定因素。
Cell Death Differ. 2011 Aug;18(8):1376-86. doi: 10.1038/cdd.2011.10. Epub 2011 Feb 18.
3
Characterization of Potent SMAC Mimetics that Sensitize Cancer Cells to TNF Family-Induced Apoptosis.强效SMAC模拟物的特性研究：使癌细胞对肿瘤坏死因子家族诱导的凋亡敏感化
PLoS One. 2016 Sep 12;11(9):e0161952. doi: 10.1371/journal.pone.0161952. eCollection 2016.
4
IAP antagonists target cIAP1 to induce TNFalpha-dependent apoptosis.IAP拮抗剂靶向cIAP1以诱导肿瘤坏死因子α依赖性凋亡。
Cell. 2007 Nov 16;131(4):682-93. doi: 10.1016/j.cell.2007.10.037.
5
Overcoming cancer cell resistance to Smac mimetic induced apoptosis by modulating cIAP-2 expression.通过调节 cIAP-2 表达克服 Smac 模拟物诱导的细胞凋亡抵抗。
Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11936-41. doi: 10.1073/pnas.1005667107. Epub 2010 Jun 14.
6
A small molecule Smac-mimic compound induces apoptosis and sensitizes TRAIL- and etoposide-induced apoptosis in breast cancer cells.一种小分子Smac模拟化合物可诱导乳腺癌细胞凋亡，并使TRAIL和依托泊苷诱导的凋亡敏感化。
Oncogene. 2005 Nov 10;24(49):7381-8. doi: 10.1038/sj.onc.1208888.
7
A Smac-mimetic sensitizes prostate cancer cells to TRAIL-induced apoptosis via modulating both IAPs and NF-kappaB.一种 Smac 模拟物通过调节 IAP 和 NF-κB 使前列腺癌细胞对 TRAIL 诱导的细胞凋亡敏感。
BMC Cancer. 2009 Nov 6;9:392. doi: 10.1186/1471-2407-9-392.
8
SMAC mimetic (JP1201) sensitizes non-small cell lung cancers to multiple chemotherapy agents in an IAP-dependent but TNF-α-independent manner.SMAC 模拟物（JP1201）以依赖 IAP 但不依赖 TNF-α的方式使非小细胞肺癌对多种化疗药物敏感。
Cancer Res. 2011 Dec 15;71(24):7640-8. doi: 10.1158/0008-5472.CAN-10-3947. Epub 2011 Nov 2.
9
Small-molecule SMAC mimetics as new cancer therapeutics.小分子SMAC模拟物作为新型癌症治疗药物。
Pharmacol Ther. 2014 Oct;144(1):82-95. doi: 10.1016/j.pharmthera.2014.05.007. Epub 2014 May 16.
10
CLL cells are resistant to smac mimetics because of an inability to form a ripoptosome complex.CLL 细胞对 SMAC 模拟物有抗性，因为它们无法形成 RIPoptosome 复合物。
Cell Death Dis. 2013 Aug 29;4(8):e782. doi: 10.1038/cddis.2013.305.
引用本文的文献
1
Parthanatos and apoptosis: unraveling their roles in cancer cell death and therapy resistance.PARP-1依赖性细胞坏死与细胞凋亡：揭示它们在癌细胞死亡和治疗抗性中的作用
EXCLI J. 2025 Mar 4;24:351-380. doi: 10.17179/excli2025-8251. eCollection 2025.
2
infection promotes TNF-α signaling and SMAC mimetic-mediated apoptosis in human prostate cancer.感染促进人前列腺癌中的肿瘤坏死因子-α信号传导和SMAC模拟物介导的细胞凋亡。
Heliyon. 2023 Oct 11;9(10):e20655. doi: 10.1016/j.heliyon.2023.e20655. eCollection 2023 Oct.
3
LCL161 enhances expansion and survival of engineered anti-tumor T cells but is restricted by death signaling.LCL161 增强了工程抗肿瘤 T 细胞的扩增和存活，但受到死亡信号的限制。
Front Immunol. 2023 Apr 17;14:1179827. doi: 10.3389/fimmu.2023.1179827. eCollection 2023.
4
Induction of Breast Cancer Cell Apoptosis by TRAIL and Smac Mimetics: Involvement of RIP1 and cFLIP.TRAIL与Smac模拟物诱导乳腺癌细胞凋亡：RIP1和cFLIP的作用
Curr Issues Mol Biol. 2022 Oct 11;44(10):4803-4821. doi: 10.3390/cimb44100327.
5
ILP-2: A New Bane and Therapeutic Target for Human Cancers.白细胞介素-2：人类癌症的新祸根与治疗靶点。
Front Oncol. 2022 Jun 23;12:922596. doi: 10.3389/fonc.2022.922596. eCollection 2022.
6
Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors.利用小分子抑制剂靶向泛素-蛋白酶体系统用于癌症治疗
Cancers (Basel). 2021 Jun 20;13(12):3079. doi: 10.3390/cancers13123079.
7
Inflammatory Pathophysiology as a Contributor to Myeloproliferative Neoplasms.炎性发病机制作为骨髓增殖性肿瘤的一个致病因素。
Front Immunol. 2021 Jun 1;12:683401. doi: 10.3389/fimmu.2021.683401. eCollection 2021.
8
cIAP1/2 are involved in the radiosensitizing effect of birinapant on NSCLC cell line in vitro.cIAP1/2参与了比瑞那潘在体外对非小细胞肺癌细胞系的放射增敏作用。
J Cell Mol Med. 2021 May 3;25(13):6125-36. doi: 10.1111/jcmm.16526.
9
Pathophysiology of Mitochondrial Dysfunction in Human Spermatozoa: Focus on Energetic Metabolism, Oxidative Stress and Apoptosis.人类精子线粒体功能障碍的病理生理学：聚焦于能量代谢、氧化应激和细胞凋亡。
Antioxidants (Basel). 2021 Apr 28;10(5):695. doi: 10.3390/antiox10050695.
10
TNF in the era of immune checkpoint inhibitors: friend or foe?免疫检查点抑制剂时代的肿瘤坏死因子：是友还是敌？
Nat Rev Rheumatol. 2021 Apr;17(4):213-223. doi: 10.1038/s41584-021-00584-4. Epub 2021 Mar 8.
本文引用的文献
1
IAP antagonists target cIAP1 to induce TNFalpha-dependent apoptosis.IAP拮抗剂靶向cIAP1以诱导肿瘤坏死因子α依赖性凋亡。
Cell. 2007 Nov 16;131(4):682-93. doi: 10.1016/j.cell.2007.10.037.
2
IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis.IAP拮抗剂可诱导c-IAPs的自身泛素化、NF-κB激活以及TNFα依赖性凋亡。
Cell. 2007 Nov 16;131(4):669-81. doi: 10.1016/j.cell.2007.10.030.
3
Autocrine TNFalpha signaling renders human cancer cells susceptible to Smac-mimetic-induced apoptosis.自分泌肿瘤坏死因子α信号使人类癌细胞对Smac模拟物诱导的凋亡敏感。
Cancer Cell. 2007 Nov;12(5):445-56. doi: 10.1016/j.ccr.2007.08.029.
4
Specificity of TRAF3 in its negative regulation of the noncanonical NF-kappa B pathway.TRAF3在其对非经典NF-κB信号通路的负调控中的特异性。
J Biol Chem. 2007 Feb 9;282(6):3688-94. doi: 10.1074/jbc.M610271200. Epub 2006 Dec 11.
5
Distinct signaling pathways in TRAIL- versus tumor necrosis factor-induced apoptosis.肿瘤坏死因子相关凋亡诱导配体（TRAIL）与肿瘤坏死因子诱导凋亡中的不同信号通路。
Mol Cell Biol. 2006 Nov;26(21):8136-48. doi: 10.1128/MCB.00257-06. Epub 2006 Aug 28.
6
The E3 ubiquitin ligase itch couples JNK activation to TNFalpha-induced cell death by inducing c-FLIP(L) turnover.E3泛素连接酶itch通过诱导c-FLIP(L)周转将JNK激活与TNFα诱导的细胞死亡联系起来。
Cell. 2006 Feb 10;124(3):601-13. doi: 10.1016/j.cell.2006.01.021.
7
A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death.一种小分子Smac模拟物可增强TRAIL和TNFα介导的细胞死亡。
Science. 2004 Sep 3;305(5689):1471-4. doi: 10.1126/science.1098231.
8
Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes.通过两个连续的信号复合物诱导肿瘤坏死因子受体I介导的细胞凋亡。
Cell. 2003 Jul 25;114(2):181-90. doi: 10.1016/s0092-8674(03)00521-x.
9
Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule.Fas利用激酶RIP作为效应分子触发一条不依赖半胱天冬酶-8的替代性细胞死亡途径。
Nat Immunol. 2000 Dec;1(6):489-95. doi: 10.1038/82732.
10
The death domain kinase RIP mediates the TNF-induced NF-kappaB signal.死亡结构域激酶RIP介导肿瘤坏死因子诱导的核因子κB信号。
Immunity. 1998 Mar;8(3):297-303. doi: 10.1016/s1074-7613(00)80535-x.
Zotero 插件