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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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The cationic polymerization mechanism consists of three steps: initiation, propagation, and termination. In the initiation step of the polymerization process, the π bond of a monomer gets protonated by the Lewis acid catalyst, which is formed from boron trifluoride and water. The protonation of the π bond generates a carbocation stabilized by the electron‐donating group. In the propagation step, the π bond of the second monomer acts as a nucleophile and attacks the...
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Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
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Chain-growth or addition polymerization is successive addition reactions of monomers with a polymer chain. In radical chain-growth polymerization, the reaction proceeds via a free-radical intermediate. The free radical is formed from radical initiators, which spontaneously generate free radicals by homolytic fission. Organic peroxides (such as dibenzoyl peroxide, as shown in Figure 1) or azo compounds are popular radical initiators. A low concentration ratio of radical initiator to monomer is...
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The radical chain-growth polymerization mechanism consists of three steps: initiation, propagation, and termination of polymerization. The polymerization initiates when a free radical generated from the radical initiator adds to the unsaturated bond in the monomer. The unpaired electron of the free radical and one π electron in the unsaturated bond creates a σ bond between the free radical and the monomer. As a result, the other π electron in the unsaturated bond converts this species into...
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  2. 小分子誘発ポリメリゼーションはbcl6の分解を誘発する
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  2. 小分子誘発ポリメリゼーションはbcl6の分解を誘発する

関連する実験動画

Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

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小分子誘発ポリメリゼーションはBCL6の分解を誘発する

Mikołaj Słabicki1,2,3, Hojong Yoon4,5, Jonas Koeppel1,2,3

  • 1Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Nature
|November 19, 2020

PubMed で要約を見る

まとめ
この要約は機械生成です。

新しい小分子BI-3802は,腫瘍性転写因子B細胞リンパ腫6 (BCL6) をポリメリ化し,細胞集積を形成させ,タンパク質分解を誘導する.

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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

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High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
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High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

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関連する実験動画

Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

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High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
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High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

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科学分野:

  • 生物化学
  • 分子生物学
  • 薬理学について

背景:

  • 標的型タンパク質の分解は がん治療における重要な課題です
  • 既存の方法は 特定のタンパク質の標的と 闘っています
  • タリドミド類は薬剤による分解の可能性を示しています.

研究 の 目的:

  • 標的型タンパク質分解のための新しいメカニズムを探求する.
  • 小分子BI-3802がBCL6に 与える影響を調べるため
  • BI-3802がタンパク質の分解を 誘導する仕組みを理解する

主な方法:

  • クリオ電子顕微鏡で 分子相互作用を可視化します
  • タンパク質のポリメリゼーションと分解を研究する生化学的測定法
  • ユビキチン化とタンパク質分解を評価するための細胞測定法.

主要な成果:

  • BI-3802はBCL6のBTBドメインに結合し,そのポリメリゼーションをフィラメントに誘導する.
  • このポリメリゼーションは,SIAH1 E3リガゼによるユビキチン化を促進する.
  • BI-3802はBCL6のタンパク質分解を誘導し,薬理学的活性を増強する.

結論:

  • 小さな分子は,ポリメリゼーションを通じて特定のタンパク質の分解を誘導することができます.
  • BI-3802は,BCL6を標的とする新しい治療戦略を表しています.
  • このアプローチは新薬開発と 合成生物学の新たな道を開きます