Programmed cell death-2 isoform1 is ubiquitinated by parkin and increased in the substantia nigra of patients with autosomal recessive Parkinson's disease
Programmed cell death-2 isoform1 is ubiquitinated by parkin and increased in the substantia nigra of patients with autosomal recessive Parkinson's disease
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DOI：
10.1016/j.febslet.2008.12.055
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发表时间：
2009-02-04
期刊：
影响因子：
3.5
通讯作者：
Hattori, Nobutaka
中科院分区：
文献类型：
--
作者：
Fukae, Jiro;Sato, Shigeto;Hattori, Nobutaka
Parkin基因突变与常染色体隐性遗传性帕金森病(Arpd)有关，其功能丧失被认为影响Parkin泛素连接酶的活性。其底物的积聚可导致ARPD黑质(SN)的多巴胺能神经变性。在这里，我们证明了parkin与程序性细胞死亡-2亚型1(PDCD2-1)相互作用，并促进其泛素化。此外，在阿尔茨海默病和散发性帕金森病的SN中也发现了PDCD2-1的积聚，这表明泛素-蛋白酶体系统的共同失效与阿尔茨海默病和散发性帕金森病的神经元死亡有关。
Mutations in parkin gene are responsible for autosomal recessive Parkinson's disease (ARPD) and its loss-of-function is assumed to affect parkin ubiquitin ligase activity. Accumulation of its substrate may induce dopaminergic neurodegeneration in the substantia nigra (SN) of ARPD. Here, we show that parkin interacts with programmed cell death-2 isoform 1 (PDCD2-1) and promotes its ubiquitination. Furthermore, accumulation of PDCD2-1 was found in the SN of ARPD as well as in sporadic PD, suggesting that common failure of the ubiquitin-proteasome system is associated with neuronal death in both ARPD and sporadic PD.