PMID: 12783850Jun 5, 2003Paper

The p38 subunit of the aminoacyl-tRNA synthetase complex is a Parkin substrate: linking protein biosynthesis and neurodegeneration

Human Molecular Genetics
Olga CortiAlexis Brice

Abstract

Parkinson's disease (PD) is a severe neurological disorder, characterized by the progressive degeneration of the dopaminergic nigrostriatal pathway and the presence of Lewy bodies (LBs). The discovery of genes responsible for familial forms of the disease has provided insights into its pathogenesis. Mutations in the parkin gene, which encodes an E3 ubiquitin-protein ligase involved in the ubiquitylation and proteasomal degradation of specific protein substrates, have been found in nearly 50% of patients with autosomal-recessive early-onset parkinsonism. The abnormal accumulation of substrates due to loss of Parkin function may be the cause of neurodegeneration in parkin-related parkinsonism. Here, we demonstrate that Parkin interacts with, ubiquitylates and promotes the degradation of p38, a key structural component of the mammalian aminoacyl-tRNA synthetase complex. We found that the ubiquitylation of p38 is abrogated by truncated variants of Parkin lacking essential functional domains, but not by the pathogenic Lys161Asn point mutant. Expression of p38 in COS7 cells resulted in the formation of aggresome-like inclusions in which Parkin was systematically sequestered. In the human dopaminergic neuroblastoma-derived SH-SY5Y cel...Continue Reading

Citations

Jan 9, 2009·Apoptosis : an International Journal on Programmed Cell Death·Tomohiro Nakamura, Stuart A Lipton
Feb 5, 2010·Apoptosis : an International Journal on Programmed Cell Death·Hansruedi Büeler
Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Hui YangSheng-Di Chen
May 25, 2012·Molecular Neurobiology·Koichi WakabayashiHitoshi Takahashi
Aug 27, 2009·Journal of Proteome Research·Zhiyin XunDavid E Clemmer
Dec 6, 2012·Nature Communications·Esther WongAna Maria Cuervo
Mar 29, 2013·Nature Communications·M Scott VandiverSolomon H Snyder
Aug 27, 2013·Nature Neuroscience·Yunjong LeeTed M Dawson
Aug 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sang Gyu ParkSunghoon Kim
Sep 9, 2010·Proceedings of the National Academy of Sciences of the United States of America·Han Seok KoTed M Dawson
Oct 31, 2009·The Journal of Biological Chemistry·Susan S Safadi, Gary S Shaw
Oct 5, 2010·The Journal of Biological Chemistry·Dong ChenGuanghui Wang
Mar 18, 2009·The Journal of Biological Chemistry·Monika KaminskaMarc Mirande
Oct 27, 2007·Antioxidants & Redox Signaling·Tomohiro Nakamura, Stuart A Lipton
Feb 27, 2009·Antioxidants & Redox Signaling·Jeanne M M TanKah-Leong Lim
May 27, 2008·Human Molecular Genetics·Esther S P WongKah-Leong Lim
Aug 31, 2006·Behavioural Pharmacology·Sheila M Fleming, Marie-Françoise Chesselet
Apr 23, 2008·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Yoshikuni MizunoHideki Mochizuki
May 4, 2012·Cold Spring Harbor Perspectives in Medicine·Casey CookLeonard Petrucelli
Nov 21, 2007·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Koichi WakabayashiHitoshi Takahashi
Dec 21, 2004·Journal of Neurochemistry·Iris H HennKonstanze F Winklhofer
Jun 15, 2005·Annual Review of Biochemistry·Mark R Cookson
Jul 19, 2005·Annual Review of Neuroscience·Darren J MooreTed M Dawson
Oct 7, 2008·Annual Review of Pharmacology and Toxicology·Alan L Schwartz, Aaron Ciechanover
Aug 16, 2006·Neuro-degenerative Diseases·Helen C Ardley, Philip A Robinson
Aug 26, 2011·The Journal of Clinical Investigation·Kye-Young KimMichael N Sack
Oct 13, 2010·Journal of Geriatric Psychiatry and Neurology·Lynn M BekrisCyrus P Zabetian
Jan 7, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Syed Z ImamSenlin Li
Jun 3, 2011·The Open Biochemistry Journal·Carolyn A RankinMark Richter
Jun 18, 2014·Orphanet Journal of Rare Diseases·Inna Bendikov-BarMia Horowitz
Apr 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Sang Gyu ParkSunghoon Kim
Jul 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Rainer Von CoellnTed M Dawson
Oct 27, 2004·Cell and Tissue Research·Rainer von CoellnTed M Dawson
Jun 7, 2011·Annual Review of Genomics and Human Genetics·Ian MartinTed M Dawson
Apr 25, 2012·Cellular and Molecular Life Sciences : CMLS·Helen Walden, R Julio Martinez-Torres
Jul 1, 2005·FEBS Letters·J C DächselT Gasser

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