Receptor-interacting protein 140 as a co-repressor of Heat Shock Factor 1 regulates neuronal stress response.

摘要: Heat shock response (HSR) is a highly conserved transcriptional program that protects organisms against various stressful conditions. However, the molecular mechanisms modulating HSR, especially suppression of poorly understood. Here, we found RIP140, wide-spectrum cofactor nuclear hormone receptors, acts as co-repressor heat factor 1 (HSF1) to suppress HSR in healthy neurons. When neurons are stressed such by or sodium arsenite (As), cells engage specific proteosome-mediated degradation reduce RIP140 level, thereby relieving and activating HSR. requires Tyr-phosphorylation Syk activated Lowering level hippocampal from As stress, significantly it increases neuron survival improves spine density. Reducing mouse rescues chronic As-induced spatial learning deficits. This first study elucidating RIP140-mediated HSF1-activated brain. Importantly, relieves this suppression, allowing efficiently timely programs recover. Therefore, stimulating activate anti-stress provides potential preventive therapeutic strategy for neurodegeneration diseases.