XIAP is not required for human tumor cell survival in the absence of an exogenous death signal.
XIAP is not required for human tumor cell survival in the absence of an exogenous death signal.
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DOI：
10.1186/1471-2407-10-11
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发表时间：
2010-01-12
期刊：
影响因子：
3.8
通讯作者：
Hager JH
中科院分区：
文献类型：
--
作者：
Sensintaffar J;Scott FL;Peach R;Hager JH
X-linked Inhibitor of Apoptosis（XIAP）作为一种肿瘤药物靶点，引起了人们的广泛关注。它是IAP家族中唯一能在体外直接抑制caspase活性的成员，并通过其C端E3泛素连接酶RING结构域调控细胞凋亡等生物学过程。然而，关于XIAP在体外正常生长条件下调节肿瘤细胞增殖和存活的作用存在争议。我们利用siRNA系统地敲低十种人肿瘤细胞系中的XIAP，然后随时间监测XIAP蛋白水平和细胞活力。为了研究XIAP在内源性与外源性细胞死亡途径中的作用，我们比较了用各种机制不同的内源性途径诱导剂或外源性途径的典型诱导剂TNF相关凋亡诱导配体（TRAIL）处理的XIAP耗尽细胞的活力。XIAP敲低对6个细胞系的生存力没有影响，而在其他4个细胞系中的影响是温和和短暂的。XIAP敲除仅使肿瘤细胞对TRAIL而不是线粒体途径诱导剂敏感。这些数据表明，XIAP在调节死亡受体介导的细胞凋亡中具有比内在途径介导的细胞死亡更重要的作用。
The X-linked Inhibitor of Apoptosis (XIAP) has attracted much attention as a cancer drug target. It is the only member of the IAP family that can directly inhibit caspase activity in vitro, and it can regulate apoptosis and other biological processes through its C-terminal E3 ubiquitin ligase RING domain. However, there is controversy regarding XIAP's role in regulating tumor cell proliferation and survival under normal growth conditions in vitro. We utilized siRNA to systematically knock down XIAP in ten human tumor cell lines and then monitored both XIAP protein levels and cell viability over time. To examine the role of XIAP in the intrinsic versus extrinsic cell death pathways, we compared the viability of XIAP depleted cells treated either with a variety of mechanistically distinct, intrinsic pathway inducing agents, or the canonical inducer of the extrinsic pathway, TNF-related apoptosis-inducing ligand (TRAIL). XIAP knockdown had no effect on the viability of six cell lines, whereas the effect in the other four was modest and transient. XIAP knockdown only sensitized tumor cells to TRAIL and not the mitochondrial pathway inducing agents. These data indicate that XIAP has a more central role in regulating death receptor mediated apoptosis than it does the intrinsic pathway mediated cell death.
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影响因子：
6.4
作者：
Lima, RT;Martins, SM;Vasconcelos, MH
通讯作者：
Vasconcelos, MH
影响因子：
4.8
作者：
Eckelman, BP;Salvesen, GS
通讯作者：
Salvesen, GS
DOI：
10.3324/haematol.13483
发表时间：
2009-01-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Desplanques, Gregoire;Giuliani, Nicola;Barille-Nion, Sophie
通讯作者：
Barille-Nion, Sophie
影响因子：
10.3
作者：
Mashima, T;Oh-Hara, T;Tsuruo, T
通讯作者：
Tsuruo, T
影响因子：
11.4
作者：
Deveraux, QL;Leo, E;Reed, JC
通讯作者：
Reed, JC