ヘリックス・ループ・ヘリックス・ファミリー・マイオジェニック・レギュレータへの反応に対する細胞史の影響
B W Schäfer1, B T Blakely, G J Darlington
1Department of Pharmacology, Stanford University School of Medicine, California 94305-5332.
Nature
|March 29, 1990
まとめ
筋肉特異的な遺伝子調節剤であるMyoDとミオジニンは,線維芽細胞における筋肉遺伝子発現を誘導するが,肝細胞では誘導できない. 細胞融合における完全な筋肉遺伝子の活性化には,線維芽細胞内の他の要因が必要である.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- 発達生物学 発達生物学とは
背景:
- 分化した細胞は,in vivoで安定した状態を維持する.
- 細胞融合は,遺伝子発現と細胞の可塑性の変化につながる可能性があります.
- 筋肉細胞やその他の細胞型から形成されたヘテロカリオンは,遺伝子発現パターンの変化を示します.
研究 の 目的:
- MyoDまたはミオジニンが,非筋肉細胞における筋肉特異的遺伝子発現を誘発できるかどうかを調査する.
- ヘテロカリオンで観察されたフェノタイプの変換におけるこれらのレギュレータの役割を決定する.
- 細胞融合中の筋肉遺伝子の活性化に必要な要因を特定する.
主な方法:
- MyoD/ミオゲニンが微量注射,転移,レトロウイルス感染を経由して線維芽細胞と肝細胞に安定して一時的に導入される.
- MyoDを発現する肝細胞と線維芽細胞の融合.
- 結果となるヘテロカリオンの筋肉特異性および肝臓特異性遺伝子発現の分析.
主要な成果:
- MyoD/myogenin発現は,線維芽細胞に筋肉特異遺伝子を誘発したが,肝細胞にはそうではなかった.
- MyoDを発現する肝細胞と線維芽細胞の融合は,ヘテロカリオン内の両方の細胞タイプで筋肉特異遺伝子を活性化させた.
- MyoD/myogeninが直接導入されたとき,肝細胞は筋肉特有の遺伝子を活性化しませんでした.
結論:
- MyoDとミオゲニンは単独では,肝細胞における筋肉特異の遺伝子発現を誘導するのに不十分です.
- 堅固な筋肉遺伝子活性化には,MyoD/myogeninに加えて,フィブロブラスト特異的要因が必要である.
- 細胞の分化状態は,細胞史とタンパク質の相互作用によって影響を受けます.
関連する概念動画
Master Transcription Regulators
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...
Mitogens and the Cell Cycle
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Lineage Commitment
Commitment is the process whereby stem cells:
Diversity in Cell Signaling Responses
The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity.
Graded and Abrupt Responses
Some signaling systems generate...
Graded and Abrupt Responses
Some signaling systems generate...
TGF - β Signaling Pathway
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...


