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相关概念视频

Cell Signaling Feedback Loops01:07

Cell Signaling Feedback Loops

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Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
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Positive and Negative Feedback Loops01:18

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Animal organs and organ systems constantly adjust to internal and external changes through a process called homeostasis ("steady state"). Examples of these changes include regulation of the level of glucose or calcium in the blood or internal responses to external temperatures. Homeostasis requires  maintaining an internal dynamic equilibrium:
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The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
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Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
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Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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In most cases, excessive hormone production is prevented by negative feedback—a loop that starts with a stimulus inducing the release of a particular substance, like a hormone, to maintain a certain level before triggering a signal that results in a decrease in further release of the hormone.
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Monitoring Protein-RNA Interaction Dynamics In Vivo at High Temporal Resolution Using χCRAC
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在NRF2-p97-NRF2负反循环中.

Aryatara Shakya1, Pengfei Liu2, Jack Godek1

  • 1Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ, 85721, USA.

Redox biology
|August 13, 2023
PubMed
概括
此摘要是机器生成的。

蛋白质p97负面调节NRF2,但NRF2也针对p97,创建一个反循环. 癌症的这种双重上调表明抑制NRF2和p97可能是治疗策略.

关键词:
亚是一种.癌症 癌症 癌症 癌症Nrf2 没有任何问题.氧化应激是一种氧化应激.蛋白质稳定性 蛋白质稳定性在P97中,P97是P97的代码.

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科学领域:

  • 细胞生物学 细胞生物学
  • 蛋白质稳定酶的分子机制
  • 氧化还原平衡 (redox homeostasis) 是一种

背景情况:

  • p97 (VCP) 是一种依赖ATP的分离酶,参与蛋白质稳定.
  • p97通过促进其蛋白质体降解来负面调节NRF2.
  • NRF2是细胞防御氧化应激的关键转录因子.

研究的目的:

  • 调查p97和NRF2.2.之间的监管关系.
  • 阐明NRF2-p97-NRF2反循环在氧化还原稳定中的作用.
  • 探索向癌症中的NRF2和p97的治疗潜力.

主要方法:

  • 通过CRISPR/Cas9基因组编辑来突变p97基因中的ARE.
  • 在工程细胞系和人类癌症患者数据中分析p97和NRF2表达.
  • 评估NRF2和p97抑制在癌细胞中的协同效应.

主要成果:

  • 鉴定出p97是NRF2的基因,建立了一个负反循环.
  • p97 ARE-突变细胞显示了改变的p97/NRF2表达和受损的NRF2反应.
  • 在人类癌症中观察到NRF2激活和p97表达之间的正相关性.
  • 联合抑制NRF2和p97协同杀死具有两者的高表达率的癌细胞.

结论:

  • 一个新的NRF2-p97-NRF2负反循环维持了氧化还原平衡.
  • NRF2和p97的双重上调与某些癌症有关.
  • 同时抑制NRF2和p97为特定癌症患者群体提供了潜在的治疗策略.