Regulation of apoptosis by extracellular molecules binding to cell @entity204 receptors has received much attention in recent years. Fas, a member of the @entity5 necrosis factor receptor superfamily, is a transmembrane protein whose extracellular domain binds its cognate ligand ( @entity12 ), which can induce apoptosis in sensitive cells. Fas ligation leads to activation of cell @entity204 proteases, thereby initiating a proteolytic cascade which results in cellular fragmentation and @entity204 . Apoptosis is also regulated by inhibitory signals which promote cell survival. The @entity588 family of proteins is composed of both inhibitors and activators of programmed cell @entity204 . The @entity588 protein itself inhibits many apoptotic stimuli while other members of the @entity588 family such as bak and bid promote cell @entity204 . Many types of @entity5 chemotherapy induce cellular stress leading to induction of apoptosis. Stress-activated protein kinases such as @entity1435 have been shown to inactivate @entity588 through phosphorylation and induce cleavage of bid. Deficiency of proapoptotic @entity588 family members has been associated with drug-resistant phenotypes. We report that exposure of @entity1 @entity957 lines to different chemotherapy drugs activates a caspase cascade which is distinct from that of receptor-mediated apoptosis. The variable sensitivity of each @entity5 cell line to different forms of chemotherapy was not due to differences in caspase or @entity588 family protein expression. Rather, the stress-activated protein kinase @entity1435 was overexpressed by resistant SCC lines which correlated with reductions in proapoptotic bid and bak protein expression. These two proteins exhibit distinct patterns of intracellular localization during chemotherapy-induced apoptosis.

A common pathway for chemotherapy-induced apoptosis in @entity1 XXXX lines distinct from that of receptor-mediated cell @entity204 .

@entity1 :: ('9606', 'Species') :: ['human'] @entity588 :: ('596', 'Gene') :: ['bcl2'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity957 :: ('MESH:D002294', 'Disease') :: ['squamous cell carcinoma'] @entity12 :: ('356', 'Gene') :: ['FasL'] @entity1435 :: ('1432', 'Gene') :: ['p38'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death']
@entity957 :: (MESH:D002294,Disease) :: ['squamous cell carcinoma']
