Identification and characterization of Ich-3, a member of the interleukin-1beta converting enzyme (ICE)/Ced-3 family and an upstream regulator of ICE.
We report here the isolation and characterization of a new member of the ice/ced-3 family of cell death genes, named ich-3. The predicted amino acid sequence of Ich-3 protein shares 54% identity with murine interleukin-1beta converting enzyme (ICE). Overexpression of ich-3 in Rat-1 and HeLa cells induces apoptosis, which can be inhibited by CrmA and Bcl-2. The mRNA and proteins of ich-3 are dramatically induced in vivo upon stimulation with lipopolysaccharide, an inducer of septic shock. The ich-3 gene product can be cleaved by cytotoxic T cells granule serine protease granzyme B, suggesting that Ich-3 may mediate apoptosis induced by granzyme B. Ich-3 does not process proIL-1beta directly but does promote proIL-1beta processing by ICE. These results suggest that Ich-3 may play a very important role in apoptosis and inflammatory responses and may be an upstream regulator of ICE.
Wang
S
S
Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown, Massachusetts 02129, USA.
Miura
M
M
Jung
Y k
Yk
Zhu
H
H
Gagliardini
V
V
Shi
L
L
Greenberg
A H
AH
Yuan
J
J
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D020170:Caspase 1; D020169:Caspases; D053471:Caspases, Initiator; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D005796:Genes; D053804:Granzymes; D007249:Inflammation; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000378:metabolism; D014018:Tissue Distribution
D017931:DNA Primers; D008070:Lipopolysaccharides; D011506:Proteins; D012333:RNA, Messenger; D053804:Granzymes; C509214:Gzmb protein, mouse; C509215:Gzmb protein, rat; D012697:Serine Endopeptidases; C101136:Casp4 protein, mouse; C491071:Casp4 protein, rat; D020169:Caspases; D053471:Caspases, Initiator; D003546:Cysteine Endopeptidases; D020170:Caspase 1