ID: 74: Interleukin-6 globally influences stress-signaling by reducing the expression of the mTOR-Inhibitor REDD1 in a STAT3-dependent manner

摘要: Mammalian target of rapamycin (mTOR) is a central mediator cellular growth and survival which potently activated by interleukin 6 (IL-6). However, the molecular mechanisms IL-6-induced mTOR activation are still poorly understood. activity negatively regulated in development DNA damage response 1 (REDD1). Expression REDD1 induced stressors such as damaging agents. Stress-induced expression facilitates repair temporarily blocking mTOR-induced signaling. reduced has been associated with proliferative diseases liver cancer. We show that IL-6. The reduction protein IL-6 independent proteasomal or caspase-mediated degradation but occurs on level mRNA. follows same kinetics activation, suggesting it contributes to activation. decrease phosphatidylinositide-3-kinase (PI3K) mitogen-activated kinase (MAPK) signaling depends signal transducer activator transcription 3 (STAT3). Consequently, inhibition STAT3 blocks Of note, beside basal also stress-induced enabling globally interfere stress-signaling. In summary, we present novel STAT3-dependent mechanism both IL-6-dependent reversion (through repression expression) might contribute inflammatory conditions.