FOXO转录因子：细胞质量控制的关键调节因子。
FOXO transcription factors: key regulators of cellular quality control.
作者信息
Webb Ashley E, Brunet Anne
机构信息
Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Department of Genetics, Stanford University, Stanford, CA 94305, USA; Glenn Laboratories for the Biology of Aging at Stanford, Stanford, CA 94305, USA.
出版信息
Trends Biochem Sci. 2014 Apr;39(4):159-69. doi: 10.1016/j.tibs.2014.02.003. Epub 2014 Mar 13.
Abstract
FOXO transcription factors are conserved regulators of longevity downstream of insulin signaling. These transcription factors integrate signals emanating from nutrient deprivation and stress stimuli to coordinate programs of genes involved in cellular metabolism and resistance to oxidative stress. Here, we discuss emerging evidence for a pivotal role of FOXO factors in promoting the expression of genes involved in autophagy and the ubiquitin-proteasome system--two cell clearance processes that are essential for maintaining organelle and protein homeostasis (proteostasis). The ability of FOXO to maintain cellular quality control appears to be critical in processes and pathologies where damaged proteins and organelles accumulate, including aging and neurodegenerative diseases.
摘要
FOXO转录因子是胰岛素信号下游保守的长寿调节因子。这些转录因子整合来自营养剥夺和应激刺激的信号，以协调参与细胞代谢和抗氧化应激的基因程序。在这里，我们讨论了新出现的证据，证明FOXO因子在促进参与自噬和泛素-蛋白酶体系统的基因表达中起关键作用，这两个细胞清除过程对于维持细胞器和蛋白质稳态（蛋白质平衡）至关重要。在受损蛋白质和细胞器积累的过程和病理状况中，包括衰老和神经退行性疾病，FOXO维持细胞质量控制的能力似乎至关重要。
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