リン酸化調節されたeIF3d変換スイッチは,細胞の代謝ストレスへの適応を媒介する
Adam M Lamper1, Rebecca H Fleming2, Kayla M Ladd2
1Department of Biology, Brandeis University, Waltham, MA 02453, USA. amysiyinglee@gmail.com.
まとめ
細胞のストレスは タンパク質合成の停止を誘発する eIF3dと呼ばれるタンパク質は,代謝ストレス中に翻訳を再プログラムし,グルコースホメオスタシス経路を制御することによって細胞の生存を助けます.
科学分野:
- 分子生物学
- 細胞 の ストレス 反応
- 代謝の調節
背景:
- 全球的なタンパク質合成は 細胞のストレスで停止します
- 特定のストレスに対して 異なる遺伝子プログラムが活性化されます
- ストレス中の選択的遺伝子発現のメカニズムは不明である.
研究 の 目的:
- 代謝ストレス反応におけるeIF3dの役割を調査する.
- 選択的な遺伝子発現のために翻訳がどのように再プログラムされているかを理解します.
- グルコース欠乏状態におけるeIF3dの細胞生存への寄与を決定する.
主な方法:
- 代謝ストレス下におけるヒト細胞におけるeIF3dの活性化を研究した.
- eIF3d 調節における CK2 リン酸化の役割を分析した.
- mTOR経路のメンバーを含む,eIF3d制御された遺伝子発現を調べた.
- 細胞生存のためのeIF3d媒介翻訳の必要性を評価した.
主要な成果:
- eIF3dは,キャップ結合タンパク質で,代謝ストレスによって活性化されます.
- eIF3dの活性化は,CK2のリン酸化減少と関連している.
- eIF3dは,グルコースホメオスタシスとmTORシグナル伝達に関与する遺伝子の翻訳を制御する.
- eIF3d依存の翻訳は,グルコース欠乏時の生存に不可欠です.
結論:
- eIF3dは,代謝ストレスに対する細胞反応の重要な調節剤として作用する.
- CK2によるeIF3dのリン酸化は,その活性を調節する.
- eIF3d媒介の選択的翻訳は,グルコースホメオスタシスの維持と細胞生存に不可欠です.
関連する概念動画
Stringent Response in E. coli
174
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
174
Other Stress Responses in Bacteria
209
Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
209
PI3K/mTOR/AKT Signaling Pathway
4.8K
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...
4.8K
The Unfolded Protein Response
6.0K
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...
6.0K
Regulation of the Unfolded Protein Response
2.8K
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...
2.8K
Translational Regulation
394
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
394


