智力障碍蛋白DDX3X的O-GlcNAcylation可以进行蛋白静态细胞循环控制
Conor W Mitchell1,2, Huijie Yuan1,2, Marie Sønderstrup-Jensen1
1Department of Molecular Biology and Genetics, Aarhus Universitet, Aarhus, Denmark.
Open biology
|July 1, 2025
概括
在Ser584的DDX3X的O-GlcNAcylation稳定了蛋白质,防止其降解. 这种蛋白静止机制对于通过控制环林E1的表达来调节细胞周期进入S阶段至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- O-GlcNAcylation是一种关键的翻译后修饰,调节细胞过程.
- 细胞周期进展对O-GlcNAc稳态敏感,但调节机制尚不清楚.
- 与小头症相关的RNA螺旋酶DDX3X在细胞循环控制中起作用.
研究的目的:
- 研究O-GlcNAcylation在调节DDX3X稳定性和细胞周期进展中的作用.
- 确定DDX3X上的特定O-GlcNAcylation位点及其功能后果.
- 阐明将O-GlcNAc修饰与细胞循环调节联系起来的蛋白静态机制.
主要方法:
- 局部特异性突变发生改变O-GlcNAcylation在Ser584的DDX3X.
- 蛋白质体降解试验以评估DDX3X的稳定性.
- 西方涂抹测量DDX3X和环素E1.1.的蛋白质水平.
- 流细胞计分析细胞周期进展.
主要成果:
- 在DDX3X的Ser584处O-GlcNAcylation的损失导致其被蛋白酶体降解的增加.
- 减少DDX3X稳定性导致其向基因,环林E1.1.表达的减少.
- 对DDX3X的O-GlcNAcylation受损导致细胞周期从G1到S阶段的进展延迟.
结论:
- DDX3X的Ser584 O-GlcNAcylation作为一种蛋白静态机制,控制其稳定性.
- 这种修改对于通过调节DDX3X水平和环林E1表达来调节S相进入至关重要.
- 在DDX3X上单个O-GlcNAc位点显著影响蛋白质稳定性和细胞周期动态.
相关概念视频
02:34Inhibition of Cdk Activity
4.9K
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...
4.9K
02:37DNA Damage can Stall the Cell Cycle
9.3K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.3K
01:23Negative Regulator Molecules
36.1K
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.
36.1K
02:23Abnormal Proliferation
4.6K
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...
4.6K
02:58Regulated Protein Degradation
7.7K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.7K
01:28The Cell Cycle Control System
3.5K
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
3.5K