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関連する概念動画

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.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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Endocrine Signaling01:45

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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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Despite the protective membrane that separates a cell from the environment, cells need the ability to detect and respond to environmental changes. Additionally, cells often need to communicate with one another. Unicellular and multicellular organisms use a variety of cell signaling mechanisms to communicate to respond to the environment.
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関連する実験動画

Updated: Feb 8, 2026

Analyzing Supercomplexes of the Mitochondrial Electron Transport Chain with Native Electrophoresis, In-gel Assays, and Electroelution
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リンパ腫における腫瘍性シグナル伝達を制御する多タンパク質超複合体

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
まとめ

新しく発見されたMy-T-BCR超複合体は,拡散型大B細胞リンパ腫 (DLBCL) の腫瘍性B細胞受容体 (BCR) 信号伝達を誘導する. この超複合体は,イブルチニブに対する反応を説明し,DLBCLサブタイプに対する標的治療を導く.

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関連する実験動画

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Analyzing Supercomplexes of the Mitochondrial Electron Transport Chain with Native Electrophoresis, In-gel Assays, and Electroelution
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科学分野:

  • 腫瘍学
  • 分子生物学
  • 免疫学

背景:

  • B細胞受容体 (BCR) 信号伝達は,B細胞リンパ腫の治療標的であるが,その抑制は,分散型大B細胞リンパ腫 (DLBCL) の患者のサブセットにのみ有益である.
  • 活性化されたB細胞型 (ABC) DLBCLサブタイプは,不良な結果を示し,NF- kBの活性化にはBCR信号に依存する.
  • CD79A,CD79B,MYD88の変異はABC DLBCLで一般的であり,MYD88 (L265P) が流行している.

研究 の 目的:

  • DLBCLにおけるBTK阻害剤イブルーチニブに対する例外的な臨床反応の分子基礎を決定する.
  • BCRシグナル依存の促進におけるCD79BとMYD88変異の協力性を解明する.
  • 分子的に定義されたDLBCLサブセットのための新しい治療戦略を特定する.

主な方法:

  • 全ゲノムCRISPR-Cas9スクリーニング
  • 機能プロテオミクス
  • 細胞線と患者の生検の分析
  • エンドリソソームのmTORによる同局化研究

主要な成果:

  • イブルチニブ反応性DLBCLにおけるMYD88,TLR9,BCRを含む多タンパク質超複合体 (My-T-BCR) の発見
  • My-T-BCR超複合体はmTORと共にエンドリソソームに同定され,生存を促すNF-κBとmTORのシグナリングを誘導する.
  • BCRとmTORのシグナル伝達を併せて抑制すると,My- T- BCR超複合体の形成と機能が相乗的に低下する.
  • My- T- BCR超複合体は,イブルーチニブに反応するDLBCLを特徴付け,応答者と非応答者を区別した.

結論:

  • My-T-BCR超複合体は,DLBCLにおける腫瘍性BCRシグナル伝達の新しいモードを表しています.
  • この超複合体は,BCRとmTOR阻害剤の結合毒性に関するメカニズム的洞察を提供します.
  • My-T-BCR超複合体は,イブルチニブ反応のバイオマーカーとして機能し,特定のDLBCLサブセットのための合理的な薬剤設計を導く.