title: α-Synuclein overexpression represses 14-3-3θ transcription.
abstract: Previous gene microarray studies have shown that expression of 14-3-3θ is significantly decreased in an α-synuclein transgenic mouse model. In this study, we tested whether α-synuclein can regulate 14-3-3θ transcription. We demonstrate that the 14-3-3θ mRNA level is decreased in SH-SY5Y cells overexpressing α-synuclein. Luciferase activity under the control of the 14-3-3θ promoter is reduced both in stable SH-SY5Y cells constitutively overexpressing α-synuclein and in doxycycline-inducible SH-SY5Y cells upon α-synuclein induction, suggesting that the regulation of 14-3-3θ by α-synuclein occurs at the transcriptional level. Knockdown of α-synuclein by RNA interference does not increase the 14-3-3θ mRNA level. These findings suggest that α-synuclein represses 14-3-3θ transcription under pathologic conditions, but that regulation of 14-3-3θ expression is not a function of endogenous α-synuclein at baseline.
authors.affiliation: Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Civitan International Research Center 560D, 1719 6th Avenue South, Birmingham, AL, 35294, USA.
authors.forename: Huiping
authors.initials: H
authors.lastname: Ding
authors.forename: Naomi S
authors.initials: NS
authors.lastname: Fineberg
authors.forename: Michelle
authors.initials: M
authors.lastname: Gray
authors.forename: Talene A
authors.initials: TA
authors.lastname: Yacoubian
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D012333:RNA, Messenger; C497604:SNCA protein, human; D051844:alpha-Synuclein
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