@entity5 overexpress members of the @entity2532 ( @entity2532 ) family. IAPs contribute to @entity5 cell apoptosis resistance by the inhibition of caspases, and are degraded by the proteasome to allow further progression of apoptosis. Here we show that @entity5 cells can alter the specificity of cytosolic proteolysis in order to acquire apoptosis resistance, which promotes formation of rapidly growing @entity5 . Survival of @entity5 cells with low proteasomal activity can occur in the presence of high expression of @entity64450 ( @entity64450 ), a large subtilisin-like peptidase that complements proteasomal activity. We find that this state leaves @entity5 cells unable of effectively degrading IAPs, and that cells in this state form rapidly growing @entity5 in vivo. We also find, in studies of apoptosis resistant cells derived from large in vivo @entity5 , that these have acquired an altered peptidase activity, with up-regulation of @entity64450 activity and decreased proteasomal activity. Importantly, we find that growth of @entity5 is limited by maintenance of the apoptosis resistant phenotype. The apoptosis resistant phenotype was reversed by increased expression of @entity17205 / @entity17205 , an antagonist of @entity2532 molecules. Our data suggest a reversible mechanism in regulation of apoptosis resistance that drives @entity5 progression in vivo. These data are relevant in relation to the multitude of therapy-resistant clinical @entity5 that have increased levels of @entity2532 molecules.

Tumors acquire XXXX ( @entity2532 )-mediated apoptosis resistance through altered specificity of cytosolic proteolysis.

@entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'subcutaneous tumors', 'Many tumors', 'tumors'] @entity2532 :: ('3375', 'Gene') :: ['IAP', 'inhibitor of apoptosis protein'] @entity17205 :: ('56616', 'Gene') :: ['DIABLO', 'Smac'] @entity64450 :: ('7174', 'Gene') :: ['Tri-peptidyl-peptidase II', 'TPP II']
@entity2532 :: (3375,Gene) :: ['inhibitor of apoptosis protein']
