相关实验视频
Updated: May 29, 2025

14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
9.5K
通过SLFN11介导的核糖体生物发生障碍会诱导TP53独立的亡
Akane Ogawa1, Keiichi Izumikawa2, Sota Tate3
1Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0017, Japan.
Molecular cell
|February 5, 2025
概括
施莱芬11 (SLFN11) 通过损害核糖体生物生成 (RiBi) - - 细胞生存至关重要的过程 - - 触发癌细胞死亡. 这种损伤会耗尽像MCL1这样的关键蛋白质,导致独立于TP53.5的亡.
科学领域:
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
- 细胞死亡机制 细胞死亡机制
背景情况:
- 核糖体生物生成 (RiBi) 对于细胞功能至关重要,在癌症中经常受到失调.
- 抑制RiBi可以触发各种细胞反应,包括细胞亡.
- 睡眠11 (SLFN11) 是一种涉及细胞应激反应的蛋白质.
研究的目的:
- 研究SLFN11在通过破坏核糖体生物生成来诱导亡中的作用.
- 阐明SLFN11影响RiBi和细胞存活的分子机制.
- 确定RiBi损伤是否是SLFN11介导的癌细胞死亡的一般机制.
主要方法:
- 在癌症细胞系中的复制应激诱导.
- 对rRNA合成和处理的分析.
- 评估RNA聚合酶I活性和染色质可访问性.
- 蛋白质耗尽研究,专注于短寿命蛋白质,如MCL1.
- 对SLFN11域的功能分析 (步行者B基因,DNA结合,脱,RNase位点).
- 直接RNA聚合酶I抑制剂和其他RiBi抑制剂的测试.
- 在一个由34个人类癌症细胞系组成的小组中进行评估.
主要成果:
- SLFN11 抑制rRNA合成和处理,导致RiBi损伤.
- 这种损伤与RNA聚合酶I的积累和增加rDNA染色质可访问性有关.
- 依赖SLFN11的RiBi损伤优先耗尽短寿命蛋白质,特别是MCL1.
- 特定的SLFN11功能域对于调解RiBi损伤至关重要.
- RiBi 损伤有效降低 MCL1 水平,并诱导TP53 独立的亡.
- 与直接RiBi抑制剂观察到相似的亡效应,无论SLFN11是否存在.
- 这些发现在34个人类癌症细胞系中得到了验证.
结论:
- 核糖体生物生成 (RiBi) 损伤是使MCL1失活并诱导亡的强有力的机制.
- SLFN11利用RiBi损伤作为一个TP53独立的前位病路径.
- 通过诱导RiBi损伤,SLFN11使癌细胞对化疗剂敏感.
- RiBi 损伤代表了癌症治疗的强大策略.
相关概念视频
Abnormal Proliferation
4.4K
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...
4.4K
The Intrinsic Apoptotic Pathway
6.2K
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...
6.2K
Riboswitches
8.0K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.0K
The Nucleolus
8.7K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
8.7K
PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K
Negative Regulator Molecules
35.1K
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.
35.1K

