The co-chaperone p23 is degraded by caspases and the proteasome during apoptosis

TY - JOUR

T1 - The co-chaperone p23 is degraded by caspases and the proteasome during apoptosis

AU - Mollerup, Jens

AU - Berchtold, Martin Werner

N1 - Keywords: Hsp90 co-chaperone; Cytosolic prostaglandin E2 synthase; Caspase-3; Caspase-8

PY - 2005

Y1 - 2005

N2 - 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 TNFa-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.

AB - 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 TNFa-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.

U2 - 10.1016/j.febslet.2005.06.045

DO - 10.1016/j.febslet.2005.06.045

M3 - Journal article

C2 - 16038904

SN - 0014-5793

VL - 579

SP - 4187

EP - 4192

JO - FEBS Letters

JF - FEBS Letters

IS - 19

ER -