cAMP-response element-binding protein and heat-shock protein 70 additively suppress polyglutamine-mediated toxicity in Drosophila

Iijima-Ando, K., Wu, P., Drier, E. A., Iijima, K., Yin, J. C. P. (July 2005) cAMP-response element-binding protein and heat-shock protein 70 additively suppress polyglutamine-mediated toxicity in Drosophila. Proc Natl Acad Sci U S A, 102 (29). pp. 10261-6. ISSN 0027-8424 (Print)

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DOI: 10.1073/pnas.0503937102


Gene-specific expansion of polyglutamine-encoding CAG repeats can cause neurodegenerative disorders, including Huntington's disease. It is believed that part of the pathological effect of the expanded protein is due to transcriptional dysregulation. Using Drosophila as a model, we show that cAMP-response element-binding protein (CREB) is involved in expanded polyglutamine-induced toxicity. A mutation in the Drosophila homolog of CREB, dCREB2, enhances lethality due to polyglutamine peptides (polyQ), and an additional copy of dCREB2 partially rescues this lethality. Neuronal expression of expanded polyQ attenuates in vivo CRE-mediated transcription of a reporter gene. As reported previously, overexpression of heat-shock protein 70 (Hsp70) rescues polyglutamine-dependent lethality. However, it does not rescue CREB-mediated transcription. The protective effects of CREB and heat-shock protein 70 against polyQ are additive, suggesting that targeting multiple pathways may be effective for treatment of polyglutamine diseases.

Item Type: Paper
Uncontrolled Keywords: Animals Cyclic AMP Response Element-Binding Protein metabolism Drosophila Drosophila Proteins genetics Gene Expression Regulation genetics HSP70 Heat-Shock Proteins metabolism Luciferases Nervous System Diseases genetics metabolism Neurons metabolism Peptides genetics metabolism Survival Analysis Trans-Activators genetics Trinucleotide Repeat Expansion genetics
Subjects: diseases & disorders > nervous system diseases and disorders
organs, tissues, organelles, cell types and functions > tissues types and functions > embryogenesis
diseases & disorders > cancer > cancer types > huntington's disease
CSHL Authors:
Communities: CSHL labs > Yin lab
Depositing User: CSHL Librarian
Date: 19 July 2005
Date Deposited: 12 Jan 2012 21:24
Last Modified: 09 Nov 2017 16:23
PMCID: PMC1177387
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