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 journalArticle

164 Citations (Scopus)

Abstract

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
Volume272
Issue number34
DOIs
StatePublished - Aug 22 1997
Externally publishedYes

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Caspase 2
Caspase 3
Caspase 1
Chemical activation
Apoptosis
Peptide Hydrolases
DNA Fragmentation
Caspases
Aldehydes
aspartyl-glutamyl-valyl-aspartal
Peptides
DNA
Processing

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Li, H., Bergeron, L., Cryns, V., Pasternack, M. S., Zhu, H., Shi, L., ... Yuan, J. (1997). Activation of caspase-2 in apoptosis. Journal of Biological Chemistry, 272(34), 21010-21017. https://doi.org/10.1074/jbc.272.34.21010

Activation of caspase-2 in apoptosis. / Li, Honglin; Bergeron, Louise; Cryns, Vince; Pasternack, Mark S.; Zhu, Hong; Shi, Lianfa; Greenberg, Arnold; Yuan, Junying.

In: Journal of Biological Chemistry, Vol. 272, No. 34, 22.08.1997, p. 21010-21017.

Research output: Contribution to journalArticle

Li, H, Bergeron, L, Cryns, V, Pasternack, MS, Zhu, H, Shi, L, Greenberg, A & Yuan, J 1997, 'Activation of caspase-2 in apoptosis', Journal of Biological Chemistry, vol. 272, no. 34, pp. 21010-21017. https://doi.org/10.1074/jbc.272.34.21010
Li H, Bergeron L, Cryns V, Pasternack MS, Zhu H, Shi L et al. Activation of caspase-2 in apoptosis. Journal of Biological Chemistry. 1997 Aug 22;272(34):21010-21017. https://doi.org/10.1074/jbc.272.34.21010
Li, Honglin ; Bergeron, Louise ; Cryns, Vince ; Pasternack, Mark S. ; Zhu, Hong ; Shi, Lianfa ; Greenberg, Arnold ; Yuan, Junying. / Activation of caspase-2 in apoptosis. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 34. pp. 21010-21017.
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