Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2006 Apr 21;22(2):269-75.
doi: 10.1016/j.molcel.2006.03.009.

The Apoptosome Activates caspase-9 by Dimerization

Affiliations

The Apoptosome Activates caspase-9 by Dimerization

Cristina Pop et al. Mol Cell. .

Abstract

The apical protease of the human intrinsic apoptotic pathway, caspase-9, is activated in a polymeric activation platform known as the apoptosome. The mechanism has been debated, and two contrasting hypotheses have been suggested. One of these postulates an allosteric activation of monomeric caspase-9; the other postulates a dimer-driven assembly at the surface of the apoptosome--the "induced proximity" model. We show that both Hofmeister salts and a reconstituted mini-apoptosome activate caspase-9 by a second-order process, compatible with a conserved dimer-driven process. Significantly, replacement of the recruitment domain of the apical caspase of the extrinsic apoptotic pathway, caspase-8, by that of caspase-9 allows activation of this hybrid caspase by the apoptosome. Consequently, apical caspases can be activated simply by directing their zymogens to the apoptosome, ruling out the requirement for allosteric activation and supporting an induced proximity dimerization model for apical caspase activation in vivo.

Similar articles

See all similar articles

Cited by 96 articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback