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相关概念视频

The Supercomplexes in the Crista Membrane01:41

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The mitochondrial cristae membrane is the primary site for the oxidative phosphorylation (OXPHOS) process of energy conversion mediated through respiratory complexes I to V. These complexes have been widely studied for decades, and it has been proven that they form supramolecular structures called respiratory supercomplexes (SC). These higher-order complexes may be crucial in maintaining the biochemical structure and improving the physiological activity of the individual complexes while...
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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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Such genes that act...
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Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
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Bacterial signaling can occur within bacteria (intracellular) or between bacteria (intercellular). At times, a group of bacteria behaves like a community. To achieve this, they engage in quorum sensing, the perception of higher cell density that causes changes in gene expression. Quorum sensing involves both extracellular and intracellular signaling. The signaling cascade starts with a molecule called an autoinducer (AI). Individual bacteria produce AIs that move out of the bacterial cell...
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Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...
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相关实验视频

Updated: Feb 8, 2026

Analyzing Supercomplexes of the Mitochondrial Electron Transport Chain with Native Electrophoresis, In-gel Assays, and Electroelution
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在淋巴瘤中控制瘤信号的多蛋白超级复合体

James D Phelan1, Ryan M Young1, Daniel E Webster1

  • 1Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Nature
|June 22, 2018
PubMed
概括

一个新发现的My-T-BCR超级复合体驱动瘤性B细胞受体 (BCR) 在扩散性大B细胞淋巴瘤 (DLBCL) 中发出信号. 这种超级复杂性解释了对ibrutinib的反应,并指导DLBCL亚型的向治疗.

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相关实验视频

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科学领域:

  • 癌症学
  • 分子生物学
  • 免疫学

背景情况:

  • B细胞受体 (BCR) 信号传递是B细胞淋巴瘤的治疗点,但其抑制仅对分散型大B细胞淋巴瘤 (DLBCL) 患者的一小部分有益.
  • 活化B细胞类 (ABC) DLBCL亚型表现不佳,依赖于BCR信号进行NF-κB激活.
  • 在ABC DLBCL中,CD79A,CD79B和MYD88的突变很常见,其中MYD88 (L265P) 是普遍存在的.

研究的目的:

  • 确定DLBCL中BTK抑制剂易布鲁替尼异常临床反应的分子基础.
  • 阐明CD79B和MYD88突变之间促进BCR信号依赖的合作.
  • 为分子定义的DLBCL子集确定新的治疗策略.

主要方法:

  • 全基因组CRISPR-Cas9查
  • 功能蛋白质组学
  • 细胞系和患者活检的分析
  • 用mTOR对内分泌体进行同位化研究

主要成果:

  • 在易布鲁替尼响应DLBCL中发现了涉及MYD88,TLR9和BCR的多蛋白超复合体 (My-T-BCR).
  • My-T-BCR超级复合体与mTOR在内分泌体上同定位,驱动支持生存的NF-κB和mTOR信号.
  • 联合抑制BCR和mTOR信号,协同减少了My-T-BCR超复合体的形成和功能.
  • My- T- BCR 超级复合体的特征是对ibrutinib反应的DLBCL,并将响应者与不响应者区分开来.

结论:

  • My-T-BCR超级复合体代表了DLBCL中瘤性BCR信号的新模式.
  • 这种超级复合物为结合BCR和mTOR抑制剂的协同毒性提供了机械洞察力.
  • My-T-BCR超级复合体作为ibrutinib反应的生物标志物,并指导特定DLBCL子集的合理药物设计.