一个与Ice/ced-3相关的基因Ich-1编码了编程细胞死亡的积极和消极调节者
1Cardiovascular Research Center, Massachusetts General Hospital-East Charlestown 02129.
Cell
|September 9, 1994
概括
研究人员确定了Ich-1基因,该基因对哺乳动物编程细胞死亡调节至关重要. 它的不同形式,Ich-1L和Ich-1S,分别促进和抑制细胞死亡,突出其在脊椎动物中的双重作用.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 线虫Caenorhabditis elegans利用 ced-3 基因进行编程细胞死亡.
- 介素-1β转化酶 (ICE) 是 ced-3 的一个哺乳动物同类.
- 了解哺乳动物细胞死亡途径在生物学和医学上至关重要.
研究的目的:
- 为了隔离和表征Ich-1基因,一个潜在的哺乳动物细胞死亡调节器.
- 为了研究不同Ich-1基因产物在编程细胞死亡中的功能作用.
主要方法:
- 基因隔离和表征.
- 对Ich-1 mRNA的替代拼接的分析.
- 在细胞系中进行过度表达研究以评估蛋白质功能.
主要成果:
- 确定了两种Ich-1mRNA物种,导致ICH-1L (435氨基酸) 和ICH-1S (312氨基酸) 蛋白质.
- ICH-1L与ICE子单位和C. elegans CED-3共享同源性.
- 过度表达ICH-1L诱导了编程细胞死亡,而ICH-1S抑制了血清剥夺诱导的细胞死亡.
结论:
- Ich-1 是一种涉及编程细胞死亡的哺乳动物基因.
- Ich-1基因在调节细胞死亡方面发挥着双重作用,既起诱导作用 (ICH-1L),又起抑制作用 (ICH-1S).
- 这些发现提供了关于脊椎动物细胞死亡的复杂机制的见解.
相关概念视频
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...


