Paraptosis: mediation by MAP kinases and inhibition by AIP-1/Alix
Paraptosis: mediation by MAP kinases and inhibition by AIP-1/Alix
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DOI：
10.1038/sj.cdd.4401465
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发表时间：
2004-10-01
影响因子：
12.4
通讯作者：
Bredesen, DE
中科院分区：
文献类型：
--
作者：
Sperandio, S;Poksay, K;Bredesen, DE
程序性细胞死亡（pcd）可分为凋亡和非凋亡两种形式。而半胱氨酸天冬氨酸特异性蛋白酶（半胱天冬酶）介导的细胞凋亡，非凋亡细胞死亡程序的介质少得多的特点。在这里，我们报告，paraptosis，一个替代的，非凋亡性细胞死亡程序，可能是由胰岛素样生长因子I受体（在其他诱导剂），有丝分裂原活化蛋白激酶（MAPK）介导的和抑制AIP-1/阿利克斯。AIP-1/阿利克斯的抑制作用对下垂是特异性的，因为细胞凋亡不受抑制。半胱天冬酶在该范例中没有被激活，半胱天冬酶抑制剂也不能有效地阻断细胞死亡。然而，MEK-2特异性抑制剂和针对c-jun N-末端激酶-1（JNK-1）的反义寡核苷酸可抑制胰岛素样生长因子I受体（IGFIR）诱导的截瘫。这些结果表明，IGFIR诱导的截瘫是由MAPK介导的，并被AIP-1/阿利克斯抑制。
Programmed cell death (pcd) may take the form of apoptotic or nonapoptotic pcd. Whereas cysteine aspartyl-specific proteases (caspases) mediate apoptosis, the mediators of nonapoptotic cell death programs are much less well characterized. Here, we report that paraptosis, an alternative, nonapoptotic cell death program that may be induced by the insulin-like growth factor I receptor ( among other inducers), is mediated by mitogen-activated protein kinases (MAPKs) and inhibited by AIP-1/Alix. The inhibition by AIP-1/Alix is specific for paraptosis since apoptosis was not inhibited. Caspases were not activated in this paradigm, nor were caspase inhibitors effective in blocking cell death. However, insulin-like growth factor I receptor (IGFIR)-induced paraptosis was inhibited by MEK-2-specific inhibitors and by antisense oligonucleotides directed against c-jun N-terminal kinase-1 (JNK-1). These results suggest that IGFIR-induced paraptosis is mediated by MAPKs, and inhibited by AIP-1/Alix.