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Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Covalently Linked Protein Regulators02:04

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
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谷氨胺的可用性调节组织中的cDC子集.

Graham P Lobel, Nanumi Han, William A Molina Arocho

    bioRxiv : the preprint server for biology
    |September 30, 2024
    PubMed
    概括

    瘤细胞耗尽了谷氨酸,使关键免疫细胞饥饿. 这项研究表明,谷氨胺缺乏会减少1型常规树突细胞 (cDC1s),阻碍抗瘤免疫力,并帮助癌症免疫逃避.

    科学领域:

    • 免疫学 免疫学 免疫学
    • 癌症新陈代谢 癌症新陈代谢
    • 细胞生物学 细胞生物学

    背景情况:

    • 瘤细胞为了生长而消耗谷氨胺,创造了一个营养缺乏的微环境.
    • 这种谷氨酸缺乏对免疫细胞,特别是树突细胞的影响尚不清楚.
    • 传统的树突细胞 (cDCs) 对于启动抗瘤免疫反应至关重要.

    研究的目的:

    • 研究瘤诱导的谷氨酸缺乏如何影响瘤微环境中的常规树突细胞 (cDCs).
    • 确定对cDC子集的特定影响,特别是对免疫学上重要的cDC1子集.
    • 阐明瘤利用谷氨酸代谢来逃避免疫监测的机制.

    主要方法:

    • 使用软组织肉瘤的小鼠模型.
    • 采用了谷氨胺抗剂和谷氨胺利用的遗传/药物抑制.
    • 分析了树突细胞子集 (cDC1和cDC2) 的频率,增殖和存活率.
    • 研究了mTOR信号通路的作用.

    主要成果:

    • 与瘤相关的谷氨酸缺乏症显著减少了常规树突细胞 (cDC) 的数量和频率.
    • 1型常规树突细胞 (cDC1s) 对谷氨酸缺乏特别敏感,增殖和存活率降低.

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  • 谷氨胺对抗性对树突细胞前体数量没有影响,这表明对cDC成熟和维护有特定影响.
  • 营养感应mTOR通路似乎参与调解谷氨胺对cDC1s的影响.
  • 结论:

    • 瘤利用谷氨胺代谢消耗瘤微环境,从而损害了关键的抗瘤免疫细胞 (如cDC1s) 的功能和生存.
    • 这种cDC1s的谷氨酸依赖性代表了瘤免疫逃避的新机制.
    • 向谷氨胺代谢有望增强抗瘤免疫力和癌症免疫疗法.