タンパク質システムのマルチスケールマップを用いた癌変異の解釈
Fan Zheng1,2, Marcus R Kelly1,2, Dana J Ramms2,3,4
1Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Science (New York, N.Y.)
|September 30, 2021
まとめ
NeSTマップを使って 選択中の395のタンパク質を マッピングしています これは突然変異が タンパク質組成に収束する方法を明らかにし 癌の進化を理解するのに役立ちます
科学分野:
- 腫瘍学とシステム生物学
- ゲノミクスとプロテオミクス
- 癌 の 進化
背景:
- 遺伝子変異がタンパク質複合体のような 細胞システムにどのように影響するか理解することは 癌の研究において極めて重要です
- これらのシステムをマッピングし,変異選択を受けているものを特定することは大きな課題です.
- 共通の細胞系に影響する 不同な変異が 癌の進行の鍵です
研究 の 目的:
- 癌のタンパク質システムの 総合的な地図を作成します
- 変異選択によるタンパク質システムを特定するための統計モデルを開発する.
- 多様な腫瘍変異が タンパク質組成に収束する方法を 明らかにするためです
主な方法:
- マルチオームの相互作用データを統合し,がんタンパク質システムの包括的な地図を作成します.
- 単一の統計モデルを開発し 変異選択によるシステムを特定しました
- 13種類の癌を分析し 特定の影響を受けたシステムを特定しました
主要な成果:
- NeST (Nested Systems in Tumors) が作られました がんタンパク質システムの地図です
- 13種類の癌で変異選択による 395の特定のシステムを特定した.
- PIK3CA-アクトミオシン複合体が信号伝達を阻害し,コラーゲン複合体が増殖を促進することを発見した.
結論:
- NeSTマップは 癌の進化における 正規のプロセスと新しい発見を統合しています
- 548の遺伝子を含んだ 潜在的な臨床バイオマーカーとして機能しています
- 異なる腫瘍変異が様々なスケールでタンパク質アセンブリに収束することを示した.
さらに関連する動画
07:47Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
1.8K
07:54Heterogeneity Mapping of Protein Expression in Tumors using Quantitative Immunofluorescence
Published on: October 25, 2011
18.8K
関連する概念動画
02:21Cancers Originate from Somatic Mutations in a Single Cell
13.3K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
13.3K
01:19Interactions Between Signaling Pathways
6.7K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.7K
03:03mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K
02:26Protein Networks
4.2K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.2K
01:07MAPK Signaling Cascades
6.5K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.5K
02:53Adaptive Mechanisms in Cancer Cells
6.0K
Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.0K