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Polyglutamine and CBP: Fatal attraction?

Nature Medicine volume 7, pages 528–530 (2001)Cite this article

The mutant proteins that cause polyglutamine disease bind CREB-binding protein (CBP), a key transcriptional co-activator for neuronal survival factors. This results in a loss of CBP-dependent transcription and may account for the neuronal degeneration associated with these diseases.

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Figure 1: Nuclear factor sequestration in polyglutamine disease.

Renee Lucas

References

  1. Paulson, H.L. & Fischbeck, K.H. Trinucleotide repeats in neurogenetic disorders. Annu. Rev. Neurosci. 19, 79–107 (1996).

    Article  CAS  Google Scholar 

  2. Preisinger, E., Jordan, B.M., Kazantsev, A. & Housman, D. Evidence for a recruitment and sequestration mechanism in Huntington's disease. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 354, 1029–1034 (1999).

    Article  CAS  Google Scholar 

  3. Nucifora, F.C. et al. Interference by huntingtin and atrophin-1 with CBP-mediated transcription leading to cellular toxicity. Science 291, 2423–2428 (2001).

    Article  CAS  Google Scholar 

  4. Kwok, R.P. et al. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature 370, 223–226 (1994).

    Article  CAS  Google Scholar 

  5. Kamei, Y. et al. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 85, 403–414 (1996).

    Article  CAS  Google Scholar 

  6. Kazantsev, A., Preisinger, E., Dranovsky, A., Goldgaber, D. & Housman, D. Insoluble detergent-resistant aggregates form between pathological and nonpathological lengths of polyglutamine in mammalian cells. Proc. Natl. Acad. Sci. USA 96, 11404–11409 (1999).

    Article  CAS  Google Scholar 

  7. McCampbell, A. et al. CREB-binding protein sequestration by expanded polyglutamine. Hum. Mol. Genet. 9, 2197–2202 (2000).

    Article  CAS  Google Scholar 

  8. Yamada, M. et al. Widespread occurrence of intranuclear atrophin-1 accumulation in the central nervous system neurons of patients with dentatorubral- pallidoluysian atrophy. Ann. Neurol. 49, 14–23 (2001).

    Article  CAS  Google Scholar 

  9. Shimohata, T. et al. Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription. Nature Genet. 26, 29–36 (2000).

    Article  CAS  Google Scholar 

  10. Steffan, J.S. et al. The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl. Acad. Sci. USA 97, 6763–6768 (2000).

    Article  CAS  Google Scholar 

  11. Boutell, J.M. et al. Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin. Hum. Mol. Genet. 8, 1647–1655 (1999).

    Article  CAS  Google Scholar 

  12. Stenoien, D.L. et al. Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone. Hum. Mol. Genet. 8, 731–741 (1999).

    Article  CAS  Google Scholar 

  13. Holbert, S. et al. The Gln-Ala repeat transcriptional activator CA150 interacts with huntingtin: Neuropathologic and genetic evidence for a role in Huntington's disease pathogenesis. Proc. Natl. Acad. Sci. USA 98, 1811–1816 (2001).

    Article  CAS  Google Scholar 

  14. Perez, M.K. et al. Recruitment and the role of nuclear localization in polyglutamine- mediated aggregation. J. Cell. Biol. 143, 1457–1470 (1998).

    Article  CAS  Google Scholar 

  15. Fernandez-Funez, P. et al. Identification of genes that modify ataxin-1-induced neurodegeneration. Nature 408, 101–106. (2000).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Neurogenetics Branch National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA

    Alexander McCampbell & Kenneth H. Fischbeck

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  1. Alexander McCampbell
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  2. Kenneth H. Fischbeck
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McCampbell, A., Fischbeck, K. Polyglutamine and CBP: Fatal attraction?. Nat Med 7, 528–530 (2001). https://doi.org/10.1038/87842

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