相关实验视频
Updated: Sep 15, 2025
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
9.7K
通过加速rRNA处理和调节RPL5-MDM2轴,hMTR4促进p53蛋白降解和瘤生长
Chen Xie1, Xin-Ling Liang2, Bin Chen2
1MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Oncology in South China, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China. xiech27@mail.sysu.edu.cn.
Cell death and differentiation
|July 12, 2025
概括
人类MTR4 (hMTR4) 蛋白质水平通过促进p53蛋白质降解,影响细胞周期控制. 提高hMTR4和RPL5的调节与癌症复发相关,这表明治疗潜力.
科学领域:
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
- 细胞生物学 细胞生物学
背景情况:
- hMTR4是一种RNA螺旋酶,也是核RNA外体的共同因子.
- 在p53通路和细胞周期控制中hMTR4的作用尚不清楚.
研究的目的:
- 研究hMTR4在p53通路和细胞周期调节中的功能.
- 阐明hMTR4影响p53蛋白水平和活性的分子机制.
- 探索hMTR4作为癌症治疗点的潜力.
主要方法:
- 在细胞模型中进行功能增益和丧失分析.
- 西方涂抹测试以评估蛋白质水平.
- 用RNA测序来分析基因表达.
- 使用小鼠异种移植模型进行的研究.
- 用MDM2抑制剂努特林-3A进行治疗.
主要成果:
- hMTR4通过促进p53无化和降解来降低p53蛋白水平和下游目标基因表达,加速细胞循环的进展.
- hMTR4促进了rRNA处理,导致rRNA增加,RPL5结合,核中RPL5封存,以及随后的MDM2-介导的p53降解.
- 通过抑制p53活动,hMTR4降低了p53目标基因mRNA水平.
- 在包括HCC在内的恶性瘤中,hMTR4和RPL5的高调经常出现,高的hMTR4与特定患者群体的HCC复发相关.
- 沉默Skiv2l2 (hMTR4同源) 抑制了异种移植的发展,而ASO介导的沉默抑制了瘤的生长.
结论:
- 通过hMTR4-rRNA-RPL5-MDM2-p53轴,hMTR4充当p53通路的新型调节者.
- hMTR4和rRNA处理是p53通路和细胞周期的关键调节者.
- 过度表达hMTR4促进瘤生长,是癌症的潜在治疗点,尤其是HCK.
相关概念视频
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
03:03mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K
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
01:22PI3K/mTOR/AKT Signaling Pathway
4.0K
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...
4.0K
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
01:22MicroRNAs
21.8K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
21.8K