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Polyglutamine represses cAMP-responsive-element-mediated transcription without aggregate formation.

Toshiaki Takahashi·Kenkichi Nozaki·Shoji Tsuji·Masatoyo Nishizawa·Osamu Onodera
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Abstract

Transcriptional dysregulation, particularly cAMP-responsive-element-mediated transcriptional repression, has been implicated in expanded polyglutamine diseases. However, it has not been clarified whether this transcriptional repression is a cause or result of neurodegeneration. Furthermore, the association between aggregates of expanded polyglutamine stretches and transcriptional repression is not clear. We established isogenic cell lines with polyglutamine stretches, which also expressed d2EGFP under the control of cAMP-responsive elements. In this system, the polyglutamine stretch repressed cAMP-responsive-element-mediated transcription without the formation of macroscopic expanded polyglutamine aggregates. Furthermore, aggregate formation did not have an adverse effect on the repression of transcriptional activity. The results demonstrated that the repression of cAMP-responsive-element-mediated transcription is an early event caused by a soluble form of polyglutamine stretch.

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Cell LineCyclic AMPCyclic AMP Response Element-Binding ProteinDiagnostic ImagingDose-Response Relationship, DrugDoxycyclineDrug InteractionsFluoresceinHumansPeptidesPromoter Regions, GeneticTime FactorsTranscription, GeneticTransfectionComparative StudyJournal ArticleResearch Support, Non-U.S. Gov't

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Toshiaki Takahashi, Kenkichi Nozaki, Shoji Tsuji, Masatoyo Nishizawa, Osamu Onodera. 2005-02-28. Polyglutamine represses cAMP-responsive-element-mediated transcription without aggregate formation.. https://doi.org/10.1097/00001756-200502280-00019

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