UNASSIGNED: The @entity3470 nucleates two complexes, namely @entity3470 complex 1 and 2 ( @entity13407 and @entity15025 ), which are implicated in cell growth, survival, metabolism, and @entity5 . Phosphorylation of the a-subunit of translation initiation factor @entity15204 at @entity563 51 (eIF2a @entity69570 ) is a key event of mRNA translation initiation and a master regulator of cell fate during cellular stress. Recent studies have implicated @entity3470 signaling in the stress response, but its connection to eIF2aS51P has remained unclear. Herein, we report that genetic as well as catalytic inhibition of @entity15025 induces @entity15204 aS51P. On the other hand, the allosteric inhibitor @entity3446 induces @entity15204 aS51P through pathways that are independent of @entity13407 inactivation. Increased @entity15204 aS51P by impaired @entity15025 depends on the inactivation of @entity584 , which primes the activation of the endoplasmic reticulum (ER)-resident kinase @entity7952 / @entity7952 . The biologic function of @entity15204 aS51P was characterized in @entity2916 ( @entity2916 )-mutant cells, which are defective in @entity15025 and @entity584 activity. @entity2916 -mutant cells exhibit increased @entity7952 activity, which is downregulated by the reconstitution of the cells with an activated form of @entity584 . Also, @entity2916 -mutant cells are increasingly susceptible to ER stress, which is reversed by @entity584 reconstitution. The susceptibility of @entity2916 -mutant cells to ER stress is further enhanced by the pharmacologic inhibition of @entity7952 or genetic inactivation of @entity15204 aS51P. Thus, the @entity7952 /eIF2aS51P arm is an important compensatory prosurvival mechanism, which substitutes for the loss of @entity584 under ER stress. IMPLICATIONS: A novel mechanistic link between @entity3470 function and protein synthesis is identified in @entity2916 -null @entity5 cells under stress and reveals potential for the development of antitumor treatments with stress-inducing chemotherapeutics. Mol Cancer Res; 13(10); 1-12.   2015 AACR.

@entity15025 Balances @entity584 Activation and @entity15204 XXXX 51 Phosphorylation to Promote Survival under Stress.

@entity15204 :: ('1965', 'Gene') :: ['eIF2'] @entity15025 :: ('74343(Tax:10090)', 'Gene') :: ['mTORC2'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer'] @entity69570 :: ('p|SUB|S|51|P', 'ProteinMutation') :: ['S51P'] @entity584 :: ('207', 'Gene') :: ['AKT1', 'AKT'] @entity13407 :: ('382056(Tax:10090)', 'Gene') :: ['mTORC1'] @entity7952 :: ('9451', 'Gene') :: ['PEK', 'PERK'] @entity3446 :: ('MESH:D020123', 'Chemical') :: ['rapamycin'] @entity3470 :: ('21977(Tax:10090)', 'Gene') :: ['mTOR'] @entity2916 :: ('MESH:D014402', 'Disease') :: ['tuberous sclerosis complex', 'TSC'] @entity563 :: ('CHEBI:17822', 'Chemical') :: ['serine']
@entity563 :: (CHEBI:17822,Chemical) :: ['Serine']
