発がん性システインに富んだLIMドメインタンパク質rbtn2は,赤色球体の発達に不可欠である
A J Warren1, W H Colledge, M B Carlton
1Medical Research Council Laboratory of Molecular Biology, Cambridge, England.
Cell
|July 15, 1994
まとめ
LIMドメインタンパク質rbtn2は,ネズミの赤血球発育に不可欠です. 欠乏すると,エリトロポエーゼがうまくいかないために胚の死亡が起こり,哺乳類の発達におけるその重要な役割を強調します.
科学分野:
- 発達生物学 発達生物学とは
- ヘマトポエーシス (血液形成) とは
- 分子遺伝学 分子遺伝学
背景:
- LIMドメインタンパク質rbtn2は,T細胞急性白血病と関連している.
- 正常な発達におけるrbtn2の生理学的役割を理解することは不可欠です.
- LIMドメインタンパク質は,細胞プロセスにおいて様々な役割を果たします.
研究 の 目的:
- エリトロイドの発達におけるrbtn2の役割を調査する.
- 哺乳類の胚形成過程におけるrbtn2の in vivo 機能を決定する.
- 血液形成におけるrbtn2の機能の基礎となる分子メカニズムを解明する.
主な方法:
- ホモジゴスなrbtn2ヌル突然変異のマウスを生成するために同種の再結合を用いた.
- 変異性胚の卵黄袋組織におけるエリソポエーゼスを分析した.
- ミュータントマウスの卵黄袋とES細胞を用いた in vitro 微分化アッセイを実施した.
主要な成果:
- rbtn2は核タンパク質で,赤血球系にインビボで発現する.
- ホモジゴス rbtn2 の無変異は,黄のエリソポエーゼスの失敗をもたらしました.
- ミュータント胚は,E10.5.5の頃に胚の死亡率を示した.
- 実験室内研究では,赤血球の分化における発達障害が確認されました.
結論:
- rbtn2は,マウスの適切な赤色球体の発達に不可欠です.
- rbtn2機能の喪失は,赤血球の形成に重大な欠陥をもたらします.
- LIMドメインのタンパク質は,哺乳類の発達中の系統特異に不可欠であり,rbtn2はGATA-1と同様の段階で作用する.
関連する概念動画
02:23Master 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...
01:46Electron Transport Chain: Complex I and II
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
01:26Receptor Tyrosine Kinases
Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...