Activation of caspase-2 in apoptosis

Honglin Li, Louise Bergeron, Vince Cryns, Mark S. Pasternack, Hong Zhu, Lianfa Shi, Arnold Greenberg, Junying Yuan

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Members of the CED-3/interleukin-1β-converting enzyme (ICE) protease (caspase) family are synthesized as proforms, which are proteolytically cleaved and activated during apoptosis. We report here that caspase-2 (ICH- 1/NEDD-2), a member of the ICE family, is activated during apoptosis by another ICE member, a caspase-3 (CPP32)-like protease(s). When cells are induced to undergo apoptosis, endogenous caspase-2 is first cleaved into three fragments of 32-33 kDa and 14 kDa, which are then further processed into 18- and 12-kDa active subunits. Up to 50 μM N-acetyl-Asp-Glu-Val-Asp- aldehyde (DEVD-CHO), a caspase-3-preferred peptide inhibitor, inhibits caspase-2 activation and DNA fragmentation in vivo, but does not prevent loss of mitochondrial function, while higher concentrations of DEVD-CHO (>50 μM) inhibit both. In comparison, although the activity of caspase-3 is very sensitive to the inhibition of DEVD-CHO (<50 nM), inhibition of caspase-3 activation as marked by processing of the pro-form requires more than 100 μM DEVD-CHO. Our results suggest that the first cleavage of caspase-2 is accomplished by a caspase-3-like activity, and other ICE-like proteases less sensitive to DEVD-CHO may be responsible for activation of caspase-3 and loss of mitochondrial function.

Original languageEnglish (US)
Pages (from-to)21010-21017
Number of pages8
JournalJournal of Biological Chemistry
Issue number34
StatePublished - Aug 22 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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