PML induces a novel caspase-independent death process
PML induces a novel caspase-independent death process
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DOI：
10.1038/3068
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发表时间：
1998-11-01
期刊：
影响因子：
30.8
通讯作者：
de Thé, H
中科院分区：
文献类型：
--
作者：
Quignon, F;De Bels, F;de Thé, H
PML核体(NBS)是由病毒和癌基因改变的核基质相关结构。我们在这里表明，PML的过度表达诱导细胞快速死亡，不依赖于从头转录和细胞周期。PML死亡涉及caspase-3激活缺失的细胞质特征，而caspase抑制剂如zVAD加速PML死亡，zVAD也加速干扰素诱导的死亡，提示PML参与了干扰素诱导的细胞凋亡。死亡效应子Bax和CDK抑制因子p27KIP1是PML招募到这些核区的新的NB相关蛋白，而急性早幼粒细胞白血病(APL)PML/RARα癌蛋白则使它们去定位。砷可增强PML、Bax和p27KIP1对NBS的靶向性，并与PML和干扰素协同诱导细胞死亡。因此，细胞死亡易感性与NE蛋白的NE募集相关。这些发现揭示了一种既不需要也不诱导caspase-3激活的新的细胞死亡途径，并表明NBS参与了细胞生存的控制。
PML nuclear bodies (NBs) are nuclear matrix-associated structures altered by viruses and oncogenes. We show here that PML overexpression induces rapid cell death, independent of de novo transcription and cell cycling. PML death involves cytoplasmic features of apoptosis in the absence of caspase-3 activation, and caspase inhibitors such as zVAD accelerate PML death, zVAD also accelerates interferon (IFN)-induced death, suggesting that PML contributes to IFN-induced apoptosis. The death effector BAX and the cdk inhibitor p27KIP1 are novel NB-associated proteins recruited by PML to these nuclear domains, whereas the acute promyelocytic leukaemia (APL) PML/RAR alpha oncoprotein delocalizes them. Arsenic enhances targeting of PML BAX and p27KIP1 to NBs and synergizes with PML and IFN to induce cell death. Thus, cell death susceptibility correlates with NE recruitment of NE proteins. These findings reveal a novel cell death pathway that neither requires nor induces caspase-3 activation, and suggest that NBs participate in the control of cell survival.