α-Synuclein Overexpression Represses 14-3-3θ Transcription

Previous gene microarray studies have shown that expression of 14-3-3 theta is significantly decreased in an alpha-synuclein transgenic mouse model. In this study, we tested whether alpha-synuclein can regulate 14-3-3 theta transcription. We demonstrate that the 14-3-3 theta mRNA level is decreased in SH-SY5Y cells overexpressing alpha-synuclein. Luciferase activity under the control of the 14-3-3 theta promoter is reduced both in stable SH-SY5Y cells constitutively overexpressing alpha-synuclein and in doxycycline-inducible SH-SY5Y cells upon alpha-synuclein induction, suggesting that the regulation of 14-3-3 theta by alpha-synuclein occurs at the transcriptional level. Knockdown of alpha-synuclein by RNA interference does not increase the 14-3-3 theta mRNA level. These findings suggest that alpha-synuclein represses 14-3-3 theta transcription under pathologic conditions, but that regulation of 14-3-3 theta expression is not a function of endogenous alpha-synuclein at baseline.