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Related Experiment Videos

CREB-binding protein sequestration by expanded polyglutamine.

A McCampbell1, J P Taylor, A A Taye

  • 1Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, Building 10, Room 3B11, Bethesda, MD 20892-1250, USA. mccampba@ninds.nih.gov

Human Molecular Genetics
|August 25, 2000
PubMed
Summary
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Spinal and bulbar muscular atrophy (SBMA) involves toxic protein aggregates. Researchers found CREB-binding protein (CBP) is sequestered in these aggregates, reducing its function and causing cell death.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disease caused by CAG repeat expansion, leading to polyglutamine tracts in proteins.
  • Nuclear dysfunction is implicated in SBMA pathogenesis due to polyglutamine expansion disrupting critical nuclear factors or processes.

Purpose of the Study:

  • To investigate the role of CREB-binding protein (CBP) in the nuclear inclusions characteristic of SBMA.
  • To determine if CBP sequestration contributes to polyglutamine-mediated toxicity.

Main Methods:

  • Utilized cell culture, transgenic mouse models, and patient tissues to examine CBP localization within nuclear inclusions.
  • Assessed soluble CBP levels and CBP mRNA expression in cells with expanded polyglutamine.

Related Experiment Videos

  • Investigated the effect of CBP over-expression on neuronal cell survival in a polyglutamine toxicity model.

    • Main Results:

    • CREB-binding protein (CBP) was found to be incorporated into nuclear inclusions in SBMA models and patient tissues.
    • CBP was also observed in nuclear inclusions in a cell culture model of spinocerebellar ataxia type 3.
    • Soluble CBP levels decreased in cells with expanded polyglutamine, despite increased CBP mRNA, suggesting sequestration.
    • Over-expression of CBP protected neuronal cells from polyglutamine-induced toxicity.

    Conclusions:

    • These findings support a CBP-sequestration model for polyglutamine expansion diseases like SBMA.
    • CBP plays a critical role in mitigating polyglutamine toxicity, and its sequestration contributes to disease pathogenesis.