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FEBS Lett. 2009 Feb 4;583(3):521-5. doi: 10.1016/j.febslet.2008.12.055. Epub 2009 Jan 13.

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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Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.


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.

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