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Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity.

Authors: Nucifora, F C  Sasaki, M  Peters, M F  Huang, H  Cooper, J K  Yamada, M  Takahashi, H  Tsuji, S  Troncoso, J  Dawson, V L  Dawson, T M  Ross, C A 
Citation: Nucifora FC, etal., Science. 2001 Mar 23;291(5512):2423-8.
Pubmed: (View Article at PubMed) PMID:11264541
DOI: Full-text: DOI:10.1126/science.1056784

Expanded polyglutamine repeats have been proposed to cause neuronal degeneration in Huntington's disease (HD) and related disorders, through abnormal interactions with other proteins containing short polyglutamine tracts such as the transcriptional coactivator CREB binding protein, CBP. We found that CBP was depleted from its normal nuclear location and was present in polyglutamine aggregates in HD cell culture models, HD transgenic mice, and human HD postmortem brain. Expanded polyglutamine repeats specifically interfere with CBP-activated gene transcription, and overexpression of CBP rescued polyglutamine-induced neuronal toxicity. Thus, polyglutamine-mediated interference with CBP-regulated gene transcription may constitute a genetic gain of function, underlying the pathogenesis of polyglutamine disorders.

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RGD Object Information
RGD ID: 13432093
Created: 2017-09-19
Species: All species
Last Modified: 2017-09-19
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.