人类细胞生存和增殖对CASP3原域的依赖性
Ebrahim Eskandari1,2, Gian Luca Negri3, Susanna Tan1
1Terry Fox Laboratory, British Columbia Cancer Research Institute, Vancouver, BC, Canada.
Cell death discovery
|February 6, 2024
概括
卡斯巴-3 (CASP3) 通过清除蛋白质聚合物来调节细胞生存和增殖,独立于其催化活性. 它的N-终端原域是人类细胞中这种必不可少的生存功能的关键.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 细胞存活和增殖对于组织发育,平衡和癌症进展至关重要.
- 酶-3 (CASP3) 主要以其在编程细胞死亡中的催化作用而闻名.
- 哺乳动物细胞中CASP3的非催化功能在很大程度上仍未被探索.
研究的目的:
- 研究CASP3在细胞存活和增殖中的潜在非催化功能.
- 确定负责这些功能的特定CASP3域.
- 阐明CASP3在细胞死亡之外的作用背后的分子机制.
主要方法:
- 在人体细胞中,lentiviral介导的短发针RNA (shRNA) 降低了CASP3.
- 使用各种CASP3蛋白结构的救援实验.
- 基于质谱的蛋白质组学和流动细胞计用于聚合分析.
主要成果:
- 显著降低CASP3水平阻止了细胞循环的进展和存活.
- 在细胞内蛋白质聚合物的清除中,CASP3起着至关重要的作用.
- 通过CASP3的生存功能和聚合物清除不需要催化活性.
- CASP3 的 N-终端原域足以实现其前存活和聚合清除功能.
结论:
- CASP3具有一种新的非催化功能,对人类细胞生存和增殖至关重要.
- 这一功能由CASP3 N-终端前域介导,涉及蛋白质聚合物的清除.
- 这些发现揭示了细胞存活和增殖的新层调节.
相关概念视频
Caspases
12.5K
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...
12.5K
Abnormal Proliferation
4.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
Molecular Factors Affecting Cell Division
3.1K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.1K
Negative Regulator Molecules
35.4K
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.
35.4K
The Intrinsic Apoptotic Pathway
6.6K
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...
6.6K
Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K


