Caspase-9 Holoenzyme Is a Specific and Optimal Procaspase-3 Processing Machine

Qian Yin, Hyun Ho Park, Jee Y. Chung, Su Chang Lin, Yu Chih Lo, Li S. da Graca, Xuejun Jiang, Hao Wu

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65 Citations (Scopus)


Caspase-9 activation is critical for intrinsic cell death. The activity of caspase-9 is increased dramatically upon association with the apoptosome, and the apoptosome bound caspase-9 is the caspase-9 holoenzyme (C9Holo). In this study, we use quantitative enzymatic assays to fully characterize C9Holo and a leucine-zipper-linked dimeric caspase-9 (LZ-C9). We surprisingly show that LZ-C9 is more active than C9Holo for the optimal caspase-9 peptide substrate LEHD-AFC but is much less active than C9Holo for the physiological substrate procaspase-3. The measured Km values of C9Holo and LZ-C9 for LEHD-AFC are similar, demonstrating that dimerization is sufficient for catalytic activation of caspase-9. The lower activity of C9Holo against LEHD-AFC may be attributed to incomplete C9Holo assembly. However, the measured Km of C9Holo for procaspase-3 is much lower than that of LZ-C9. Therefore, in addition to dimerization, the apoptosome activates caspase-9 by enhancing its affinity for procaspase-3, which is important for procaspase-3 activation at the physiological concentration.

Original languageEnglish
Pages (from-to)259-268
Number of pages10
JournalMolecular Cell
Issue number2
Publication statusPublished - 2006 Apr 21

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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