Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 8 August 2000
Vol. 2000, Issue 44, p. tw10
[DOI: 10.1126/stke.2000.44.tw10]

EDITORS' CHOICE

Apoptosis Hsp70 Inhibits Apaf-1-Mediated Caspase Activation

One apoptotic cascade involves the release of cytochrome c from the mitochondria, which promotes the activation of caspase-9 by the cytosolic apoptotic protease-activating factor (Apaf-1) through the formation of a large oligomeric structure called the apoptosome. Two groups (Beere et al. and Saleh et al.) show that heat shock protein 70 (Hsp70) can inhibit the activation of caspase-9 by the Apaf-1 apoptosome in vivo and in vitro. However, the data are conflicting about the exact mechanism of inhibition. Beere et al. provide evidence in vitro for Hsp70 specifically blocking the recruitment of procaspase-9 to the apoptosome without disrupting the ability of cytochrome c and Apaf-1 to form the oligomeric apoptosome. Saleh et al. have in vitro and in vivo data that suggest that Hsp70 blocks the formation of the apoptosome in an ATP-dependent manner by interacting with the CARD domain of Apaf-1 and, thus, inhibits caspase activation and apoptosis. Hsp70 does not compete for the CARD domain of Apaf-1 in the experiments by Beere et al. Thus, Hsp70 is an apoptotic inhibitor that blocks Apaf-1-mediated apoptosis, but the exact mechanism remains to be unambiguously established.

Beere, H.M., Wolf, B.B., Cain, K., Mosser, D.D., Mahboubi, A., Kuwana, T., Tailor, P., Morimoto, R.I., Cohen, G.M., and Green, D.R. (2000) Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome. Nature Cell Biol. 2: 469-475. [Online Journal]

Saleh, A., Srinivasula, S.M., Balkir, L., Robbins, P.D., and Alnemri, E.S. (2000) Negative regulation of the Apaf-1 apoptosome by Hsp70. Nature Cell Biol. 2: 476-483. [Online Journal]

Citation: Hsp70 Inhibits Apaf-1-Mediated Caspase Activation. Sci. STKE 2000, tw10 (2000).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882