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関連する概念動画

Properties of Transition Metals02:58

Properties of Transition Metals

29.7K
Transition metals are defined as those elements that have partially filled d orbitals. As shown in Figure 1, the d-block elements in groups 3–12 are transition elements. The f-block elements, also called inner transition metals (the lanthanides and actinides), also meet this criterion because the d orbital is partially occupied before the f orbitals.
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Phase Transitions02:31

Phase Transitions

22.8K
Whether solid, liquid, or gas, a substance's state depends on the order and arrangement of its particles (atoms, molecules, or ions). Particles in the solid pack closely together, generally in a pattern. The particles vibrate about their fixed positions but do not move or squeeze past their neighbors. In liquids, although the particles are closely spaced, they are randomly arranged. The position of the particles are not fixed—that is, they are free to move past their neighbors to...
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Transcription Factors02:16

Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Master Transcription Regulators02:23

Master Transcription Regulators

7.7K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Transcription01:10

Transcription

155.8K
Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
155.8K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

8.7K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
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Induction and Analysis of Epithelial to Mesenchymal Transition
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ATRはRループに対抗し転写再プログラムを可能にすることで上皮間葉転換を保護する

Parasvi S Patel1, Jacob P Matson1, Xiaojuan Ran2

  • 1Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, United States of America.

The Journal of clinical investigation
|January 22, 2026
PubMed
まとめ
この要約は機械生成です。

癌細胞の可塑性を標的とすることは重要である。この研究は、ATRキナーゼ阻害がEMTのような細胞状態遷移を破壊し、癌細胞を不安定化させることによって腫瘍の成長と転移を減少させることを明らかにする。

キーワード:
癌細胞生物学腫瘍学

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科学分野:

  • 癌生物学
  • 分子腫瘍学
  • ゲノム不安定性

背景:

  • 癌細胞の可塑性は、転写再プログラムによって駆動され、転移と治療抵抗性を促進する。
  • 上皮間葉転換（EMT）のような細胞状態遷移は、腫瘍の進行に重要である。
  • これらの遷移の治療的標的化は、大部分未踏のままである。

研究 の 目的:

  • 細胞状態遷移を治療的に標的とできるかどうかを調査する。
  • EMT中の転写再プログラムの調節におけるATRキナーゼの役割を解明する。
  • 癌治療としてのATR阻害の可能性を決定する。

主な方法:

  • 上皮間葉転換（EMT）をモデルシステムとして利用した。
  • EMT中のゲノム不安定性に対するATR阻害の影響を調査した。
  • SNAI1遺伝子座におけるRループ形成、転写複製衝突、および遺伝子調節を分析した。

主要な成果:

  • 細胞状態遷移中の転写再プログラムは、Rループと転写複製衝突を介してゲノム不安定性を誘発する。
  • ATRキナーゼは細胞状態遷移に不可欠であり、ゲノムの完全性を保護し、転写再プログラムを可能にする。
  • EMT中のATR阻害は、ゲノム不安定性を増大させ、転写再プログラムを破壊し、SNAI1におけるRループ関連DNA損傷を高める。
  • ATR阻害はSNAI1およびその他のEMT遺伝子の発現を抑制し、インビボでの腫瘍の成長と転移を減少させる。

結論:

  • ATRキナーゼは、ゲノムの完全性を維持し、転写再プログラムを促進することによって細胞状態遷移を保護する。
  • ATR阻害は、癌の可塑性を標的とし、腫瘍の進行を抑制するための有望な治療戦略を表す。
  • ATRを標的とすることは、EMTを起こしている癌細胞を排除でき、転移と治療抵抗性と戦うための新しいアプローチを提供する。
  • 癌生物学、分子腫瘍学、ゲノム不安定性