Ice/ced-3に関連する遺伝子であるIch-1は,プログラム細胞死の陽性および負のレギュレータの両方をコードする
1Cardiovascular Research Center, Massachusetts General Hospital-East Charlestown 02129.
Cell
|September 9, 1994
まとめ
研究者らは,哺乳類のプログラム細胞死調節に不可欠なIch-1遺伝子を特定しました. その異なる形態であるIch-1LとIch-1Sは,それぞれ細胞死を促進し,抑制し,脊椎動物における二重の役割を強調しています.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
- 細胞生物学 細胞生物学
背景:
- ネマトドのCaenorhabditis elegansは,プログラムされた細胞死のために ced-3遺伝子を利用しています.
- インタールイキン-1β変換酵素 (ICE) は,セド-3の哺乳類同型である.
- 哺乳類の細胞死経路を理解することは,生物学と医学において極めて重要です.
研究 の 目的:
- 哺乳類の潜在的な細胞死調節体であるIch-1遺伝子を分離し,特徴づけること.
- プログラム細胞死における異なるIch-1遺伝子産物の機能的役割を調査する.
主な方法:
- 遺伝子隔離と特徴づけ.
- Ich-1 mRNAの代替スプライシングの分析.
- タンパク質の機能を評価するために,細胞系における過剰発現の研究.
主要な成果:
- 2つのIch-1 mRNA種が特定され,ICH-1L (435アミノ酸) とICH-1S (312アミノ酸) タンパク質に至った.
- ICH-1Lは,ICEサブユニットとC. elegans CED-3とのホモロジーを共有しています.
- ICH-1Lの過剰発現はプログラム細胞死を誘発し,ICH-1Sは血清欠乏による細胞死を抑制した.
結論:
- Ich-1は,プログラムされた細胞死に関与する哺乳類の遺伝子です.
- Ich-1遺伝子は,細胞死を調節する上で二重の役割を果たし,誘発体 (ICH-1L) と抑制体 (ICH-1S) とともに作用する.
- これらの発見は,脊椎動物のプログラム細胞死亡の複雑なメカニズムについての洞察を提供します.
関連する概念動画
Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...


