title: The co-chaperone p23 is degraded by caspases and the proteasome during apoptosis.
abstract: The heat shock protein 90 co-chaperone p23 has recently been shown to be up-regulated in cancer cells and down-regulated in atheroschlerotic plaques. We found that p23 is degraded during apoptosis induced by several stimuli, including Fas and TNFalpha-receptor activation as well as staurosporine treatment. Caspase inhibition protected p23 from degradation in several cell lines. In addition, recombinant caspase-3 and 8 cleaved p23 at Asp 142 generating a degradation product of 18 kDa as seen in apoptotic cells. Truncated p23 is further degraded in a proteasome dependent process during apoptosis. Furthermore, we found that the anti-aggregating activity of truncated p23 was reduced compared to full length p23 indicating that caspase mediated p23 degradation contributes to protein destabilisation in apoptosis.
authors.affiliation: Institute of Molecular Biology and Physiology, Department of Molecular Cell Biology, University of Copenhagen, Oester Farimagsgade 2A, 1353 Copenhagen K, Denmark. jmollerup@my.molbio.ku.dk
authors.forename: Jens
authors.initials: J
authors.lastname: Mollerup
authors.forename: Martin W
authors.initials: MW
authors.lastname: Berchtold
mesh_terms: D000818:Animals; D020169:Caspases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D019746:Intramolecular Oxidoreductases; D019169:Jurkat Cells; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D041681:NIH 3T3 Cells; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D000071876:Prostaglandin-E Synthases; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D015853:Cysteine Proteinase Inhibitors; D018832:Molecular Chaperones; D010750:Phosphoproteins; D011994:Recombinant Proteins; D020169:Caspases; D046988:Proteasome Endopeptidase Complex; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases