@entity522 ( @entity4669 ) is processed by upstream caspases to @entity9287 and @entity9289 subunits, which heterodimerize. Concomitant with formation of the active heterotetramer, @entity9289 is autoprocessed to @entity14848 . Treatment of HL-60 cells with @entity16628 , a selective inhibitor of the proteasome, exponentially increased @entity522 -like hydrolytic activity and induced apoptosis but had little or no effect on the activity of upstream @entity8186 , @entity8187 , or @entity10807 . @entity16628 treatment decreased the @entity4669 zymogen and evoked the accumulation of the @entity14848 and @entity9287 subunits. Treatment of transfected @entity1 retinoblast 911 cells with a proteasome inhibitor evoked the accumulation of epitope-tagged @entity9287 , @entity14848 , and @entity9289 but had no effect on @entity4669 zymogen. This result suggests that @entity522 subunits, in contrast to the zymogen, are unstable because of degradation by the ubiquitin-proteasome system. Ubiquitin conjugates of @entity9287 and @entity14848 accumulated in cells that were cotransfected with @entity9287 and a caspase inactive mutant of @entity14848 . Substitution of @entity369 for all eight lysines of @entity9287 almost abolished its ubiquitination. Any single @entity376 or @entity376 pair was sufficient for @entity9287 ubiquitination. @entity16628 treatment of HL-60 cells induced proteolytic processing of the @entity9846 ( @entity9846 ) and decreased full-length @entity9846 , which is known to have ubiquitin-protein ligase activity for active @entity522 . These findings indicate that @entity522 subunits can be degraded by the ubiquitin-proteasome system and suggest that @entity16628 induces apoptosis in part by disabling the ubiquitin-protein ligase function of @entity9846 and by stabilizing active @entity522 subunits.

Preservation of @entity522 subunits from degradation contributes to apoptosis evoked by @entity16628 : any single @entity376 or XXXX pair of the small subunit is sufficient for ubiquitination.

@entity1 :: ('9606', 'Species') :: ['human'] @entity522 :: ('836', 'Gene') :: ['caspase-3', 'Procaspase-3'] @entity9846 :: ('331', 'Gene') :: ['XIAP', 'X-linked inhibitor of apoptosis'] @entity14848 :: ('653820', 'Gene') :: ['p17'] @entity10807 :: ('3002', 'Gene') :: ['granzyme B'] @entity8186 :: ('841', 'Gene') :: ['caspase-8'] @entity8187 :: ('842', 'Gene') :: ['caspase-9'] @entity4669 :: ('3622', 'Gene') :: ['p32'] @entity376 :: ('CHEBI:25094', 'Chemical') :: ['lysine'] @entity9289 :: ('51673', 'Gene') :: ['p20'] @entity9287 :: ('56655', 'Gene') :: ['p12'] @entity369 :: ('CHEBI:29016', 'Chemical') :: ['arginine'] @entity16628 :: ('MESH:C067713', 'Chemical') :: ['Lactacystin', 'lactacystin']
@entity376 :: (CHEBI:25094,Chemical) :: ['lysine']
