Journal of Molecular Neuroscience

, Volume 46, Issue 2, pp 303–314

The Small Chaperone Protein p23 and Its Cleaved Product p19 in Cellular Stress

  • Karen S. Poksay
  • Surita Banwait
  • Danielle Crippen
  • Xiao Mao
  • Dale E. Bredesen
  • Rammohan V. Rao
Article

Abstract

The presence of misfolded proteins elicits cellular responses including an endoplasmic reticulum (ER) stress response that may protect cells against the toxic buildup of misfolded proteins. Accumulation of these proteins in excessive amounts, however, overwhelms the “cellular quality control” system and impairs the protective mechanisms designed to promote correct folding and degrade misfolded proteins, ultimately leading to organelle dysfunction and cell death. Studies from multiple laboratories have identified the roles of several ER stress-induced cell death modulators and effectors. Earlier, we reported the role of the small co-chaperone protein p23 in preventing ER stress-induced cell death. p23 undergoes caspase-dependent cleavage to yield a 19-kD product (p19), and mutation of this caspase cleavage site not only blocks the formation of the 19-kD product but also attenuates the ER stress-induced cell death process triggered by various stressors. Thus, a critical question is whether p23 and/or p19 could serve as an in vivo marker for neurodegenerative diseases featuring misfolded proteins and cellular stress. In the present study, we used an antibody that recognizes both p23 and p19 as well as a specific neo-epitope antibody that detects only the p19 fragment. These antibodies were used to detect the presence of both these proteins in cells, primary neurons, brain samples from a mouse model of Alzheimer’s disease (AD), and fixed human AD brain samples. While patients with severe AD did display a consistent reduction in p23 levels, our inability to observe p19 in mouse or human AD brain samples suggests that the usefulness of the p23 neo-epitope antibody is restricted to cells and primary neurons undergoing cellular stress.

Keywords

Endoplasmic reticulum p23 HSP90 Alzheimer’s disease ER stress Caspase Programmed cell death 

Abbreviations

ER

Endoplasmic reticulum

pcd

Programmed cell death

AD

Alzheimer’s disease

GRP

Glucose-regulated protein

MEF

Mouse embryonic fibroblasts

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Karen S. Poksay
    • 1
  • Surita Banwait
    • 1
  • Danielle Crippen
    • 1
  • Xiao Mao
    • 1
  • Dale E. Bredesen
    • 1
    • 2
  • Rammohan V. Rao
    • 1
  1. 1.The Buck Institute for Research on AgingNovatoUSA
  2. 2.University of CaliforniaSan FranciscoUSA

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