The roles of poly(ADP-ribose)-metabolizing enzymes in alkylation-induced cell death
The roles of poly(ADP-ribose)-metabolizing enzymes in alkylation-induced cell death
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DOI：
10.1007/s00018-008-7516-5
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发表时间：
2008-02-01
影响因子：
8
通讯作者：
Althaus, F. R.
中科院分区：
文献类型：
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作者：
Cohausz, O.;Blenn, C.;Althaus, F. R.
聚 (ADP-核糖) (PAR) 已被确定为凋亡诱导因子 (AIF) 上游的 DNA 损伤诱导细胞死亡信号。 PAR 导致 AIF 从线粒体易位到细胞核并引发细胞死亡。在活细胞中，PAR 分子会因内部和外部应激因素而发生动态变化。利用RNA干扰（RNAi），我们确定了聚（ADP-核糖）聚合酶-1和-2（PARP-1、PARP-2）和聚（ADP-核糖）糖水解酶（PARG）（构成PAR分子的关键酶）在烷化剂诱导的细胞死亡中的作用。我们发现 PARP-1（而非 PARP-2 和 PARG）导致烷基化诱导的细胞死亡。同样，AIF 易位仅受 PARP-1 影响。 PARP-1 似乎在将 PAR 配置为涉及 AIF 易位的死亡信号方面发挥着重要作用，无论涉及何种死亡途径。
Poly(ADP-ribose) (PAR) has been identified as a DNA damage-inducible cell death signal upstream of apoptosis-inducing factor (AIF). PAR causes the translocation of AIF from mitochondria to the nucleus and triggers cell death. In living cells, PAR molecules are subject to dynamic changes pending on internal and external stress factors. Using RNA interference (RNAi), we determined the roles of poly(ADP-ribose) polymerases-1 and -2 (PARP-1, PARP-2) and poly(ADP-ribose) glycohydrolase (PARG), the key enzymes configuring PAR molecules, in cell death induced by an alkylating agent. We found that PARP-1, but not PARP-2 and PARG, contributed to alkylation-induced cell death. Likewise, AIF translocation was only affected by PARP-1. PARP-1 seems to play a major role configuring PAR as a death signal involving AIF translocation regardless of the death pathway involved.