転写調節体のK29関連ウビキチネーションは,展開されたタンパク質応答における細胞増殖を制御する

Qiushuang Zhang¹, Xucong Teng^2,1,3, Yicong Dai^2,1

¹New Cornerstone Science Laboratory, Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing, 100084, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|August 30, 2025

まとめ

非正規のK29結合ユビキチン鎖は,展開タンパク質応答 (UPR) 中の遺伝子転写を調節する. 細胞増殖遺伝子をダウンレギュレーションして,転写開始を妨害する.

科学分野:

細胞生物学
分子生物学
遺伝学

背景:

ユビキチン鎖は様々な機能がありますが,K29結合鎖は十分に理解されていません.
展開されたタンパク質応答 (UPR) は,精密な調節によって,内プラズマの網膜のストレスを管理する.
Ubiquitinの役割は,UPRにおけるタンパク質の分解を超えて,活発な研究分野である.

研究の目的:

K29結合ユビキチン鎖の非正規的機能を調査する.
UPR中の転写調節におけるK29結合ユビキチン鎖の役割を調査する.
細胞のストレス反応におけるコヘシンユビキチネーションの規制メカニズムを解明する.

主な方法:

展開タンパク質応答 (UPR) の誘導
コヘシン複合タンパク質 (SMC1AとSMC3) のK29結合ユビキチン化の分析
細胞増殖に関連する遺伝子の転写調節の評価 (SERTAD1,NUDT16L1).

主要な成果:

SMC1AとSMC3のK29結合ユビキチネーションは,UPR誘導時に増加する.
K29結合コヘシンユビキチネーションは細胞増殖遺伝子の転写を調節する.
増加したK29結合コヘシンユビキチネーションは,転写開始複合体の形成を妨げます.

結論:

K29に結合したユビキチン鎖は,UPR中の転写調節に重要な役割を果たします.
コヘシンユビキチネーションは,ERストレスに対する遺伝子発現を制御する重要なメカニズムです.
この発見は,ストレス下での細胞増殖に影響を与える新しい調節経路を明らかにしています.

キーワード:

さらに関連する動画

10:55

Purification of Ubiquitinated p53 Proteins from Mammalian Cells

Published on: March 21, 2022

2.3K

09:00

Detection of Protein Ubiquitination

Published on: August 19, 2009

43.0K

関連する概念動画

01:31

Regulation of the Unfolded Protein Response

2.6K

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...

2.6K

01:37

The Unfolded Protein Response

5.1K

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...

5.1K

02:04

Covalently Linked Protein Regulators

7.1K

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....

7.1K

01:23

Regulation of Expression at Multiple Steps

994

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...

994

01:22

PI3K/mTOR/AKT Signaling Pathway

3.9K

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...

3.9K

01:23

Negative Regulator Molecules

35.9K

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.