About: The deubiquitinase USP15 antagonizes Parkin-mediated mitochondrial ubiquitination and mitophagy

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About: The deubiquitinase USP15 antagonizes Parkin-mediated mitochondrial ubiquitination and mitophagy Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	The deubiquitinase USP15 antagonizes Parkin-mediated mitochondrial ubiquitination and mitophagy
Creator	Vandenberghe, Wim Gevaert, Kris Cornelissen, Tom De Strooper, Bart Haddad, Dominik »more»
source	PMC
abstract	Loss-of-function mutations in PARK2, the gene encoding the E3 ubiquitin ligase Parkin, are the most frequent cause of recessive Parkinson's disease (PD). Parkin translocates from the cytosol to depolarized mitochondria, ubiquitinates outer mitochondrial membrane proteins and induces selective autophagy of the damaged mitochondria (mitophagy). Here, we show that ubiquitin-specific protease 15 (USP15), a deubiquitinating enzyme (DUB) widely expressed in brain and other organs, opposes Parkin-mediated mitophagy, while a panel of other DUBs and a catalytically inactive version of USP15 do not. Moreover, knockdown of USP15 rescues the mitophagy defect of PD patient fibroblasts with PARK2 mutations and decreased Parkin levels. USP15 does not affect the ubiquitination status of Parkin or Parkin translocation to mitochondria, but counteracts Parkin-mediated mitochondrial ubiquitination. Knockdown of the DUB CG8334, the closest homolog of USP15 in Drosophila, largely rescues the mitochondrial and behavioral defects of parkin RNAi flies. These data identify USP15 as an antagonist of Parkin and suggest that USP15 inhibition could be a therapeutic strategy for PD cases caused by reduced Parkin levels.
has issue date	2014-10-01(xsd:dateTime)
bibo:doi	10.1093/hmg/ddu244
bibo:pmid	24852371
has license	no-cc
sha1sum (hex)	56fdeea87e316a9074d2650c8a7080d2335af5a0
schema:url	https://doi.org/10.1093/hmg/ddu244
resource representing a document's title	The deubiquitinase USP15 antagonizes Parkin-mediated mitochondrial ubiquitination and mitophagy
has PubMed Central identifier	PMC7108632
has PubMed identifier	24852371
schema:publication	Hum Mol Genet
resource representing a document's body	covid:56fdeea87e316a9074d2650c8a7080d2335af5a0#body_text
is schema:about of	named entity 'MEDIATED' named entity 'defects' named entity 'selective' named entity 'mutations' named entity 'reduced' »more»

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