Rck/p54 interacts with APP mRNA as part of a multi-protein complex and enhances APP mRNA and protein expression in

Oleg Broytman1, Pamela R Westmark, Zafer Gurel

  • 1Department of Pathology and Laboratory Medicine, Neuroscience Training Program, Waisman Center for Developmental Disabilities and Institute on Aging, University of Wisconsin, Madison, 1500 Highland Avenue, Madison, WI 53705, USA.

Neurobiology of Aging
|April 2, 2008
PubMed

Insights

Researchers identified six proteins that bind to APP mRNA, including rck/p54. Overexpressing rck/p54 increases amyloid precursor protein (APP) and mRNA levels, suggesting a new Alzheimer's disease (AD) regulatory pathway.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Alzheimer's disease (AD) is linked to amyloid precursor protein (APP) and beta-amyloid overproduction.
  • The 3'-untranslated region (UTR) of APP mRNA contains regulatory elements, including a 52-base element (52sce).
  • The 52sce element is known to bind uncharacterized cytoplasmic proteins.

Purpose of the Study:

  • To identify proteins that bind to the 52sce element of APP mRNA.
  • To investigate the interactions of these proteins with each other and with APP mRNA.
  • To explore the role of these proteins in the post-transcriptional regulation of APP.

Main Methods:

  • Protein purification and identification of specific binders to the 52sce.
  • Co-immunoprecipitation assays to study protein-protein and protein-RNA interactions in neuroblastoma cells.
  • Overexpression studies of identified proteins (e.g., rck/p54) to assess effects on APP mRNA and protein levels.

Main Results:

  • Six proteins specifically binding to the 52sce were purified and identified.
  • These identified proteins form complexes with each other and with APP mRNA in intact cells.
  • Overexpression of the DEAD-box helicase rck/p54 led to increased levels of APP mRNA and protein.

Conclusions:

  • A novel complex of six proteins, including rck/p54, specifically binds to the 52sce of APP mRNA.
  • These proteins are involved in the post-transcriptional regulation of APP.
  • This discovery suggests a new mechanism contributing to Alzheimer's disease pathogenesis.

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