DataSheet1_The environmental stress response regulates ribosome content in cell cycle-arrested S. cerevisiae.pdf

Prolonged cell cycle arrests occur naturally in differentiated cells and in response to various stresses such as nutrient deprivation or treatment with chemotherapeutic agents. Whether and how cells survive prolonged cell cycle arrests is not clear. Here, we used S. cerevisiae to compare physiological cell cycle arrests and genetically induced arrests in G1-, meta- and anaphase. Prolonged cell cycle arrest led to growth attenuation in all studied conditions, coincided with activation of the Environmental Stress Response (ESR) and with a reduced ribosome content as determined by whole ribosome purification and TMT mass spectrometry. Suppression of the ESR through hyperactivation of the Ras/PKA pathway reduced cell viability during prolonged arrests, demonstrating a cytoprotective role of the ESR. Attenuation of cell growth and activation of stress induced signaling pathways also occur in arrested human cell lines, raising the possibility that the response to prolonged cell cycle arrest is conserved.

细胞周期持续阻滞现象天然存在于分化细胞中，也可因多种应激因素诱导产生，例如营养剥夺或化疗药物处理。目前尚不明确细胞能否以及如何在长期细胞周期阻滞中存活。本研究以酿酒酵母（S. cerevisiae）为模型，对比生理状态下的细胞周期阻滞与G1期、中期及后期的基因诱导型细胞周期阻滞。长期细胞周期阻滞在所有受试条件下均会引发细胞生长衰减，同时伴随环境应激反应（Environmental Stress Response，ESR）的激活，以及经全核糖体纯化与TMT质谱分析法检测得到的核糖体含量降低。通过过度激活Ras/PKA信号通路抑制ESR，会降低细胞在长期阻滞状态下的存活率，由此证实了ESR的细胞保护功能。在阻滞状态的人类细胞系中，同样观察到细胞生长衰减与应激诱导信号通路激活的现象，这提示长期细胞周期阻滞的应答反应具有进化保守性。