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, 29 August 2000
Vol. 2000, Issue 47, p. tw6
[DOI: 10.1126/stke.2000.47.tw6]


Apoptosis Dimerized DIABLO is "Smac" Dab in the Middle of Apoptosis

Apoptosis is a highly regulated process of programmed cell death (PCD). During apoptosis, Smac/DIABLO, along with cytochrome c, is released from mitochondria. Smac/DIABLO is an apoptosis-promoting protein that interferes with the ability of inhibitors of apoptosis proteins (IAPs) to block PCD. Chai et al. now uncover the mechanism by which Smac/DIABLO exerts its effects. It was previously reported that Smac/DIABLO promotes the cleavage of procaspase-3. Chai et al. demonstrated that Smac/DIABLO induced the catalytic activity of mature, cleaved caspase-3. Smac/DIABLO function depended on its ability to homodimerize; Smac/DIABLO mutants that remain monomeric did not promote caspase-3 activation. Similarly, monomeric Smac/DIABLO mutants could not bind to the BIR2 domain of X-linked IAP, suggesting that homodimerized Smac/DIABLO exerts its effects by binding certain IAPs and preventing those IAPs from blocking caspase maturation and activation. The NH2-terminus of Smac/DIABLO was shown to be crucial for blocking IAP function, and specifically, peptides consisting of the first seven NH2-terminal amino acids from Smac/DIABLO were able to promote the activation of procaspase-3 by blocking X-linked IAP function.

Chai, J., Du, C., Wu, J.-W., Kyin, S., Wang, X., and Shi, Y. (2000) Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Nature 406: 855-862. [Online Journal]

Citation: Dimerized DIABLO is "Smac" Dab in the Middle of Apoptosis. Sci. STKE 2000, tw6 (2000).

To Advertise     Find Products

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