Programmed cell death-2 isoform1 is ubiquitinated by parkin and increased in the substantia nigra of patients with autosomal recessive Parkinson’s disease

Fukae, Jiro; Sato, Shigeto; Shiba, Kahori; Sato, Ken-ichi; Mori, Hideo; Sharp, Philip A; Mizuno, Yoshikuni; Hattori, Nobutaka

doi:10.1016/j.febslet.2008.12.055

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Volume 583, Issue 3 , Pages 521-525, 4 February 2009

Programmed cell death-2 isoform1 is ubiquitinated by parkin and increased in the substantia nigra of patients with autosomal recessive Parkinson’s disease

Edited by Jesus Avila

Jiro Fukae
- Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan
Shigeto Sato
- Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan
Kahori Shiba
- Research Institute for Diseases of Old Ages, Juntendo University School of Medicine, Tokyo, Japan
Ken-ichi Sato
- Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan
Hideo Mori
- Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan
Philip A Sharp
- Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139-4307, USA
Yoshikuni Mizuno
- Research Institute for Diseases of Old Ages, Juntendo University School of Medicine, Tokyo, Japan
Nobutaka Hattori
- Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan
- Corresponding author. Fax: +81 3 5800 0547.

Received 16 November 2008; received in revised form 9 December 2008; accepted 17 December 2008. published online 13 January 2009.

Abstract

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.

Structured summary:

MINT-6805975, MINT-6806032, MINT-6806051, MINT-6806070:

PDCD2 (uniprotkb:Q16342) physically interacts (MI:0218) with Parkin (uniprotkb:O60260) by anti tag coimmunoprecipitation (MI:0007)

MINT-6805947:

Parkin (uniprotkb:O60260) physically interacts (MI:0218) with PDCD2 (uniprotkb:Q16342) by two hybrid (MI:0018)

MINT-6806000: PDCD2 (uniprotkb:Q16342) physically interacts (MI:0218) with ubiquitin (uniprotkb:P62988) by anti tag coimmunoprecipitation (MI:0007).

Keywords: Parkin, PDCD2-1, Apoptosis, Ubiquitin-proteasome system, Substantia nigra