RRC ID 32389
著者 Min B, Kwon YC, Choe KM, Chung KC.
タイトル PINK1 phosphorylates transglutaminase 2 and blocks its proteasomal degradation.
ジャーナル J Neurosci Res
Abstract Parkinson's disease (PD) is characterized by progressive dopaminergic neuronal loss and the formation of abnormal protein aggregates, referred to as Lewy bodies (LBs). PINK1 is a serine/threonine protein kinase that protects cells from stress-induced mitochondrial dysfunction. PINK1 gene mutations cause one form of autosomal recessive early-onset PD. Transglutaminase 2 (TG2) is an intracellular protein cross-linking enzyme that has an important role in LB formation during PD pathogenesis. This study identifies PINK1 as a novel TG2 binding partner and shows that PINK1 stabilizes the half-life of TG2 via inhibition of TG2 ubiquitination and subsequent proteasomal degradation. PINK1 affects TG2 stability in a kinase-dependent manner. In addition, PINK1 directly phosphorylates TG2 in carbonyl cyanide m-chlorophenyl hydrazine-induced mitochondrial damaged states, thereby enhancing TG2 accumulation and intracellular protein cross-linking products. This study further confirms the functional link between upstream PINK1 and downstream TG2 in Drosophila melanogaster. These data suggest that PINK1 positively regulates TG2 activity, which may be closely associated with aggresome formation in neuronal cells.
巻・号 93(5)
ページ 722-35
公開日 2015-5-1
DOI 10.1002/jnr.23535
PMID 25557247
MeSH Animals Carbonyl Cyanide m-Chlorophenyl Hydrazone / pharmacology Cell Line Drosophila melanogaster Enzyme Activation / drug effects GTP-Binding Proteins / chemistry GTP-Binding Proteins / genetics GTP-Binding Proteins / metabolism* Humans Immunoprecipitation Mice Mice, Transgenic Organelles / metabolism Point Mutation / genetics Proteasome Endopeptidase Complex / genetics Proteasome Endopeptidase Complex / metabolism* Protein Glutamine gamma Glutamyltransferase 2 Protein Kinases / genetics Protein Kinases / metabolism* Protein Structure, Tertiary / physiology Proton Ionophores / pharmacology RNA Interference RNA, Messenger / metabolism Transfection Transglutaminases / chemistry Transglutaminases / genetics Transglutaminases / metabolism* Ubiquitination / drug effects Ubiquitination / genetics
IF 4.699
引用数 8
WOS 分野 NEUROSCIENCES
リソース情報
ショウジョウバエ 4523R-4 7356R-1