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関連する概念動画

Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

2.5K
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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Nuclear Export of mRNA02:31

Nuclear Export of mRNA

7.9K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.9K
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

10.9K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.9K
Nuclear Export01:42

Nuclear Export

3.8K
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
3.8K
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

4.9K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.9K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

4.0K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
4.0K

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関連する実験動画

Updated: Sep 29, 2025

Assays for the Degradation of Misfolded Proteins in Cells
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Assays for the Degradation of Misfolded Proteins in Cells

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核特異タンパク質の分解のためのメチルリーダータンパク質のハイジャック

Dhanusha A Nalawansha1, Ke Li1, John Hines1

  • 1Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06511, United States.

Journal of the American Chemical Society
|March 21, 2022
PubMed
まとめ

研究者はメチルリーダー-E3リガゼ複合体をハイジャックし,標的型タンパク質分解ツールを拡張して,新しいPROTACを開発しました. このアプローチは,FKBP12やBRD2のような標的タンパク質の核特異的な分解を可能にします.

さらに関連する動画

Reporter-based Growth Assay for Systematic Analysis of Protein Degradation
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Reporter-based Growth Assay for Systematic Analysis of Protein Degradation

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Cell-Type Specific Protein Purification and Identification from Complex Tissues Using a Mutant Methionine tRNA Synthetase Mouse Line
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Cell-Type Specific Protein Purification and Identification from Complex Tissues Using a Mutant Methionine tRNA Synthetase Mouse Line

Published on: April 13, 2022

3.0K

関連する実験動画

Last Updated: Sep 29, 2025

Assays for the Degradation of Misfolded Proteins in Cells
10:56

Assays for the Degradation of Misfolded Proteins in Cells

Published on: August 28, 2016

12.2K
Reporter-based Growth Assay for Systematic Analysis of Protein Degradation
07:47

Reporter-based Growth Assay for Systematic Analysis of Protein Degradation

Published on: November 6, 2014

10.8K
Cell-Type Specific Protein Purification and Identification from Complex Tissues Using a Mutant Methionine tRNA Synthetase Mouse Line
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Cell-Type Specific Protein Purification and Identification from Complex Tissues Using a Mutant Methionine tRNA Synthetase Mouse Line

Published on: April 13, 2022

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科学分野:

  • 生物化学
  • 分子生物学
  • 薬物の発見

背景:

  • Proteolysis-Targeting Chimeras (PROTACs) を用いた標的型タンパク質分解 (TPD) は,疾患に関連するタンパク質を制御するための重要な戦略である.
  • TPDの現在のツールボックスには,利用可能なE3リガゼ:リガンドペアの希少性があります.

研究 の 目的:

  • メチルリーダー:E3リガゼ複合体を利用してタンパク質の分解を誘導する新しい方法を導入する.
  • L3MBTL3メチルリーダー:E3リガゼ複合体を標的型タンパク質分解のために採用するPROTACの設計と評価.

主な方法:

  • L3MBTL3メチルリーダをCul4DCAF5 E3リガゼ複合体に誘導するためのPROTACを設計・合成した.
  • 核特異のタンパク質の分解を誘発する新しいPROTACの生物学的活動を評価した.

主要な成果:

  • L3MBTL3:Cul4DCAF5複合体を活用した,成功裏に設計されたPROTAC.
  • 新型PROTACを用いた標的タンパク質FKBP12とBRD2の核特異的な分解が実証された.

結論:

  • メチルリーダーに関連したE3リガゼ複合体をハイジャックすることは,PROTACの開発のためのE3リガゼレパートリーを拡大するための一般化可能な戦略を提供します.
  • このアプローチは薬剤発見における標的型タンパク質分解の可能性を広げています