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alpha-Synuclein forms a complex with transcription factor Elk-1.

A Iwata·S Miura·I Kanazawa·M Sawada·N Nukina
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Abstract

alpha-Synuclein has been identified as a component of Lewy bodies in Parkinson's disease and diffuse Lewy body disease, and glial cytoplasmic inclusions (GCIs) in multiple system atrophy (MSA). To explore the role of alpha-synuclein in the pathogenesis, we searched for molecules interacting with alpha-synuclein and discovered that GCIs are stained by anti-Elk-1 antibody. To seek the role of Elk-1 in synucleinopathies, we cotransfected alpha-synuclein and Elk-1 to cultured cells, and found small granular structure complexes where the two molecules colocalized. Moreover, alpha-synuclein and Elk-1 were co-immunoprecipitated from the cell lysates. For formation of the complex, the presence of both ETS and B-box domains of Elk-1 was required. Although there was no evidence of direct binding between alpha-synuclein and Elk-1, we discovered that alpha-synuclein and Elk-1 both bind to ERK-2, a MAP kinase. The effect of alpha-synuclein on the MAP kinase pathway was assessed using the Pathdetect system, which showed prominent attenuation of Elk-1 phosphorylation with alpha-synuclein, and especially A53T mutant. Our results suggest that alpha-synuclein reacts with the MAP kinase pathway, which might cause dysfunction of neurons and oligodendrocytes and lead to neurodegeneration in Parkinson's disease and MSA.

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Amino Acid MotifsAnimalsBinding SitesCell LineCytoplasmic GranulesDNA-Binding ProteinsHumansLewy Body DiseaseMAP Kinase Signaling SystemMacromolecular SubstancesMiceMitogen-Activated Protein Kinase 1Multiple System AtrophyMutagenesis, Site-DirectedNerve Tissue ProteinsNeurogliaNeuronsParkinson DiseasePhosphorylationPrecipitin TestsProtein BindingProtein Structure, TertiaryProto-Oncogene ProteinsSynucleinsTranscription FactorsTransfectionalpha-Synucleinets-Domain Protein Elk-1Journal Article

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A Iwata, S Miura, I Kanazawa, M Sawada, N Nukina. 2001. alpha-Synuclein forms a complex with transcription factor Elk-1.. https://doi.org/10.1046/j.1471-4159.2001.t01-1-00232.x

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