人类乳头瘤病毒E6蛋白功能的调节,通过一种新型的全素结合酶FBXO4进行调节
Arushi Vats1,2, Luca Braga2, Nezka Kavcic1
1Tumour Virology, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
mBio
|December 17, 2024
概括
研究人员将FBXO4确定为一种针对人类乳头瘤病毒 (HPV) E6降解的新型泛素化酶. 击败FBXO4和E6AP会增加HPV E6水平,并诱导癌细胞死亡,为HPV相关癌症提供新的治疗点.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 病毒学 病毒学
背景情况:
- 人类乳头瘤病毒 (HPV) E6coprotein被E6相关蛋白 (E6AP) 稳定,促进癌症的发展.
- 在没有E6AP的情况下调节HPV E6稳定性的其他乌比奎丁连酶的作用尚不清楚.
- 了解这些调节机制对于开发针对性治疗HPV相关癌症至关重要.
研究的目的:
- 为了识别新型的泛素酶,调节HPV E6稳定性独立于E6AP.
- 为了研究在与HPV相关的宫癌细胞中鉴定出ubiquitin结合酶的作用.
- 探索针对HPV相关癌症的治疗潜力,以准这些结合酶.
主要方法:
- 在CRISPR编辑的E6AP-knockout HEK293细胞中显示高通量siRNA库屏幕,表达GFP标记的HPV-18E6.6.
- 在宫癌细胞系中鉴定出 ubiquitin 酶的验证.
- 评估HPV-18E6蛋白水平和细胞死亡在E6AP和已识别的酶的联合淘汰后.
主要成果:
- 一个屏幕识别了几种泛素连接酶,在淘汰后,在没有E6AP的情况下增加HPV-18E6的表达.
- 验证了FBXO4作为一种关键的泛素酶,向HPV E6进行降解.
- 结合FBXO4和E6AP的敲除,显著增加了内源性HPV-18E6水平,并在HeLa细胞中诱导了p53-依赖的细胞死亡.
结论:
- FBXO4是一种新型的泛素酶,以一种独立于E6AP的方式准HPV E6进行降解.
- FBXO4,E6AP和p53之间的相互作用对于调节HPV阳性宫癌细胞中的细胞存活至关重要.
- 向FBXO4和E6AP是HPV相关癌症的潜在治疗策略.
关键词:
E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E6 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7 E7E6AP E6AP E6AP E6AP E6AP E6AP E6AP E6AP E6AP E6AP E6AP E6AP E6AP E6AP在FBXO4中,FBXO4是FBXO4.这是一个HPVHPVHPV.相关概念视频
Covalently 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
Receptor Downregulation in MVBs
2.0K
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...
2.0K
Regulated Protein Degradation
7.1K
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...
7.1K
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
Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K
Anaphase Promoting Complex
2.8K
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...
2.8K


