TY - JOUR
T1 - Activation of caspase-2 in apoptosis
AU - Li, Honglin
AU - Bergeron, Louise
AU - Cryns, Vince
AU - Pasternack, Mark S.
AU - Zhu, Hong
AU - Shi, Lianfa
AU - Greenberg, Arnold
AU - Yuan, Junying
PY - 1997/8/22
Y1 - 1997/8/22
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.272.34.21010
DO - 10.1074/jbc.272.34.21010
M3 - Article
C2 - 9261102
AN - SCOPUS:0030881653
SN - 0021-9258
VL - 272
SP - 21010
EP - 21017
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 34
ER -