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.
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Acknowledgments
We would like to thank Mary Ballestas and the UAB Neuroscience Core Center (P30 NS47466) for preparing the pLKO.1 control and α-syn shRNA lentiviruses, and the doxycycline-inducible α-syn pSLIK lentivirus. Consultative services on biostatistics were supported by the National Center for Advancing Translational Research of the NIH under award number UL1TR00165. The research reported in the publication was supported by the NINDS of the NIH under award number NS060948 and by the Parkinson's Association of Alabama.
Conflict of Interest
Huiping Ding, Naomi Fineberg, and Michelle Gray have no conflict of interest to declare. Talene Yacoubian declares that she has US Patent # 7,919,262 on the use of 14-3-3s in neurodegeneration.
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Ding, H., Fineberg, N.S., Gray, M. et al. α-Synuclein Overexpression Represses 14-3-3θ Transcription. J Mol Neurosci 51, 1000–1009 (2013). https://doi.org/10.1007/s12031-013-0086-5
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DOI: https://doi.org/10.1007/s12031-013-0086-5