在调节 lysosomal 和 autophagy 基因方面,USF2 和 TFEB 在竞争
Jaebeom Kim1, Young Suk Yu1, Yehwa Choi1
1Creative Research Initiatives Center for Epigenetic Code and Diseases, School of Biological Sciences, Seoul National University, Seoul, South Korea.
Nature communications
|September 27, 2024
概括
科学家们发现,在富含营养的条件下,上游刺激因子2 (USF2) 抑制了溶酶体和自基因. 这种通过酸化调节的抑制,为相关疾病提供了潜在的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 自和溶酶体通路对于细胞平衡和新陈代谢至关重要.
- 虽然有研究过功能障碍,但过度活化对恒温稳定的影响却不太清楚.
- 营养物质的可用性信号调节这些必不可少的细胞过程.
研究的目的:
- 阐明了 lysosomal 和 autophagy 基因的转录抑制机制.
- 为了确定参与控制这些途径在营养丰富条件下的关键调节者.
- 探索针对 lysosomal 和 autophagy 基因调节的治疗策略.
主要方法:
- 研究了上游刺激因子2 (USF2) 在调节 lysosomal 基因中的作用.
- 使用染色体免疫沉 (ChIP) 来评估USF2和HDAC1与CLEAR动机的结合.
- 分析了基因组乙化 (H3K27ac) 和染色质可访问性.
- 研究了USF2和转录因子EB (TFEB) 在饥饿状态下的竞争.
- 评估了GSK3β介导酸化在USF2 S155.5.的作用.
主要成果:
- 与HDAC1结合的USF2与溶酶体基因中的CLEAR基因结合,降低了基因素乙化和可访问性,从而降低了基因表达的调节.
- 在饥饿状态下,USF2与TFEB的酸化依赖的竞争调节了DNA结合.
- 在S155处USF2的GSK3β介导酸化控制其DNA结合活性和抑制功能.
- 在营养丰富的条件下,USF2介导的抑制被认为是关键的调节机制.
结论:
- USF2 作为 lysosomal 和 autophagy 基因的转录抑制剂,特别是在营养充足的情况下.
- 酸化USF2对于其对营养可用性的调节功能至关重要.
- 向USF2抑制为溶酶体和自相关疾病,包括蛋白质聚合疾病提供了一个有希望的治疗途径.
相关概念视频
01:36Delivery Pathways to the Lysosome
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Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
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01:27Autophagy
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Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
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01:22Lysosomal Hydrolases
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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
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01:13The Proteasome
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Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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01:31Lysosomes
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Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...
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02:04Covalently Linked Protein Regulators
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These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
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