通过准BubR1以实现由ubiquitin介导的降解,FBXW7调节了线性进展
Vishnu M Nair1, Amit Santhu Sabu1, Ahmed Hussain1
1School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Vithura, Thiruvananthapuram, Kerala, 695551, India.
Cellular and molecular life sciences : CMLS
|November 26, 2023
概括
SCF-FBXW7结合酶降解了BubR1,控制了轴组合检查点 (SAC). 这一过程通过调节BubR1和CENP-E在kinetochore中的稳定性来确保精确的染色体分离.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 忠实的染色体分离对于细胞分裂至关重要.
- 螺旋组装检查点 (SAC) 通过延迟异相来防止错误.
- 精确调节SAC蛋白质至关重要,但尚未完全理解.
研究的目的:
- 调查E3泛素酶SCF-FBXW7在调节组合检查点 (SAC) 中的作用.
- 阐明控制SAC蛋白质稳定性的机制,特别是BubR1.1.
主要方法:
- 人类细胞中FBXW7的耗尽.
- 对BubR1和CENP-E蛋白水平和局部性的分析.
- 立方体检测测试. 在线检测.
- 在BubR1酸化位点的位点定向突变发生.
- 在Cdk1抑制实验中.
主要成果:
- 耗尽FBXW7导致由于BubR1在kinetochores的稳定而导致长期的转相停止.
- 与BubR1相互作用的蛋白CENP-E也显示出稳定性.
- FBXW7调解了BubR1的无处不在和降解以及一个依赖BubR1.1的CENP-E域.
- 在Thr 620处BubR1的Cdk1酸化作为FBXW7.7.的降解信号.
结论:
- SCF-FBXW7是SAC的关键调节者,控制了BubR1和CENP-E在kinetochore中的稳定性.
- 上游BubR1的Cdk1酸化信号FBXW7启动降解,从而调节检查点活动.
相关概念视频
02:58Regulated Protein Degradation
7.3K
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...
7.3K
00:50Anaphase Promoting Complex
2.9K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.9K
01:15Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K
02:04Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
01:45Destabilization of Microtubules
2.7K
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.7K
01:13The Proteasome
851
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
851