Department of Pathology and Laboratory Medicine, College of Medicine and the Center for Cancer Research, University of Tennessee Health Science Center, Room 318, 19 South Manassas, Memphis, TN, 38163, USA.
Curr Genet. 2021 Oct;67(5):707-713. doi: 10.1007/s00294-021-01180-5. Epub 2021 Mar 31.
The cellular response to environmental exposures, such as nutrient shifts and various forms of stress, requires the integration of the signaling apparatus that senses these environmental changes with the downstream gene regulatory machinery. Delineating this molecular circuitry remains essential for understanding how organisms adapt to environmental flux, and it is critical for determining how dysregulation of these mechanisms causes disease. Ccr4-Not is a highly conserved regulatory complex that controls all aspects of the gene expression process. Recent studies in budding yeast have identified novel roles for Ccr4-Not as a key regulator of core nutrient signaling pathways that control cell growth and proliferation, including signaling through the mechanistic target of rapamycin complex 1 (TORC1) pathway. Herein, I will review the current evidence that implicate Ccr4-Not in nutrient signaling regulation, and I will discuss important unanswered questions that should help guide future efforts to delineate Ccr4-Not's role in linking environmental signaling with the gene regulatory machinery. Ccr4-Not is highly conserved throughout eukaryotes, and increasing evidence indicates it is dysregulated in a variety of diseases. Determining how Ccr4-Not regulates these signaling pathways in model organisms such as yeast will provide a guide for defining how it controls these processes in human cells.
细胞对外界环境暴露（如营养物质变化和各种形式的压力）的反应需要整合感知这些环境变化的信号装置与下游基因调控机制。阐明这种分子电路仍然是理解生物体如何适应环境波动的关键，对于确定这些机制的失调如何导致疾病也至关重要。Ccr4-Not 是一个高度保守的调控复合物，控制着基因表达过程的各个方面。最近在 budding yeast 中的研究发现了 Ccr4-Not 作为调控核心营养信号通路的关键调节剂的新作用，这些通路控制细胞生长和增殖，包括通过机械靶标雷帕霉素复合物 1 (TORC1) 通路的信号转导。在此，我将回顾目前的证据，表明 Ccr4-Not 参与了营养信号调节，并讨论了重要的未解决问题，这些问题应该有助于指导未来的努力，以阐明 Ccr4-Not 在将环境信号与基因调控机制联系起来方面的作用。Ccr4-Not 在真核生物中高度保守，越来越多的证据表明它在各种疾病中失调。确定 Ccr4-Not 如何在酵母等模式生物中调节这些信号通路，将为确定它如何在人类细胞中控制这些过程提供指导。
