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Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

2.1K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
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Exon Recombination02:32

Exon Recombination

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The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon...
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Complementation Tests00:49

Complementation Tests

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A complementation test is a simple cross to identify whether the two mutations are located on the same gene or different genes. It was first performed by Edward Lewis in the 1940s while working on fruit flies. He developed the test to identify the location and arrangement of different mutations on chromosomes.
Organisms heterozygous for different mutations are crossed pairwise in all combinations. If present on different genes, the mutations can complement each other by providing the missing...
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Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

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Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
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Mapping and Application of Enhancer-trap Flippase Expression in Larval and Adult Drosophila CNS
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Mapping and Application of Enhancer-trap Flippase Expression in Larval and Adult Drosophila CNS

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胚とリンパ球におけるFADDとRIP1の機能的補完

Haibing Zhang1, Xiaohui Zhou, Thomas McQuade

  • 1Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.

Nature
|March 4, 2011
PubMed
まとめ

FAS関連死亡領域 (FADD) タンパク質は,胚形成とリンパ球の機能に不可欠です. RIP1キナーゼとの相互作用により,プログラム細胞死 (アポトーシス) とネクロシスの両方を意外に調節し,発達と免疫反応に影響を与えます.

科学分野:

  • 細胞生物学 細胞生物学
  • 免疫学 免疫学とは
  • 発達生物学 発達生物学とは

背景:

  • FAS関連死亡領域 (FADD) タンパク質は,死亡受容体経由でのアポトーシスシグナル伝達において重要なアダプタである.
  • 免疫ホメオスタシスには不可欠ですが,胚形成とリンパ球の増殖におけるFADDの役割は不明です.
  • FADDは,死滅とNF-κBの活性化を調節するRIP1キナーゼと相互作用します.

研究 の 目的:

  • FADDとRIPの間の in vivo 機能的相互作用を明らかにするために1.
  • 胚形成とリンパ球の増殖におけるFADDとRIP1の役割を調査する.
  • FADD と RIP1.1 の間の細胞タイプ特有の相互作用を理解するために.

主な方法:

  • Fadd (((-/-) Rip1 (((-/-) のダブルノックアウトマウスの生成.
  • ノックアウトモデルにおける胚の発達とリンパ球の増殖の分析.
  • 細胞死経路 (アポトーシス,ネクロシス) とNF-κB活性に関する評価.

主要な成果:

  • Fadd(-/-) の胚は,高いRIP1レベルと大量死滅を示しています.
  • RIP1欠乏症は,Faddのマウスの胚死亡率を救出しました.

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  • FADDの消去は,Rip1(-/-) リンパ球における発達障害を部分的に修正し,T細胞の増殖を回復したが,B細胞の増殖は回復しなかった.
  • ダブル・ノックアウトのT細胞は,死亡受容体誘発のアポトーシスに抵抗性を示し,NF-κBの活性が低下した.
  • 結論:

    • FADDとRIP1は,アポトーシスとネクロシスを調節する重要な,細胞型特異的な相互作用を持っています.
    • この相互作用は,胚の発達とリンパ球の機能に不可欠です.
    • この発見は,細胞死と免疫反応を制御する新しいメカニズムを明らかにしている.