UNASSIGNED: Neuronal stress or injury results in the activation of proteins, which regulate the balance between survival and apoptosis. However, the complex mechanism of cell signaling involving cell death and survival, activated in response to cellular stress is not yet completely understood. To bring more clarity about these mechanisms, a Boolean network was constructed that represented the apoptotic pathway in neuronal cells. @entity9699 and @entity851 factor (NGF) were considered as inputs in the absence and presence of @entity1457 proteins known to shift the balance toward survival by rescuing pro-apoptotic cells. The probabilities of survival, DNA repair and apoptosis as cellular fates, in the presence of either the growth factor or @entity9699 , revealed a survival bias encoded in the network. Boolean predictions tested by measuring the mRNA level of @entity185 , @entity4699 , and @entity1380 in neuronal Neuro2a (N2a) cell line with NGF and @entity9699 as external input, showed positive correlation with the observed experimental results for survival and apoptotic states. It was observed that @entity187 contributed more toward rescuing cells from apoptosis in comparison to @entity23312 , @entity68339 , and @entity68340 . Overexpression of @entity187 in N2a transfected cells showed reversal of cellular fate from @entity9699 -induced apoptosis to survival. Further, the pro-survival role of the proteins @entity1379 , @entity37788 , cFLIP, and NFkB determined by vertex perturbation analysis was experimentally validated through protein inhibition experiments using EM20-25, @entity33576 and @entity46148 , which resulted in 1.27-, 1.26-, and 1.46-fold increase in apoptosis of N2a cells. The existence of a one-to-one correspondence between cellular fates and attractor states shows that Boolean networks may be employed with confidence in qualitative analytical studies of biological networks.

XXXX mediates survival in apoptotic cells-Boolean network prediction and experimental validation.

@entity1380 :: ('12028(Tax:10090)', 'Gene') :: ['BAX'] @entity851 :: ('MESH:D006130', 'Disease') :: ['neurotrophic growth'] @entity46148 :: ('MESH:C051122', 'Chemical') :: ['Wedelolactone'] @entity1457 :: ('MESH:D012769', 'Disease') :: ['heat shock'] @entity33576 :: ('MESH:C010945', 'Chemical') :: ['Embelin'] @entity185 :: ('12367(Tax:10090)', 'Gene') :: ['caspase-3'] @entity4699 :: ('12370(Tax:10090)', 'Gene') :: ['caspase-8'] @entity68339 :: ('81489(Tax:10090)', 'Gene') :: ['HSP40'] @entity187 :: ('15511(Tax:10090)', 'Gene') :: ['HSP70'] @entity68340 :: ('111042(Tax:10090)', 'Gene') :: ['HSP90'] @entity9699 :: ('14103(Tax:10090)', 'Gene') :: ['FasL'] @entity1379 :: ('12043(Tax:10090)', 'Gene') :: ['BCL2'] @entity37788 :: ('15601(Tax:10090)', 'Gene') :: ['IAP'] @entity23312 :: ('15507(Tax:10090)', 'Gene') :: ['HSP27']
@entity187 :: (15511(Tax:10090),Gene) :: ['HSP70']
