管理十种人类癌症类型中蛋白质丰富性的主调节者
Zishan Wang1, Megan Wojciechowicz1, Jordan Rosen1
1Department of Genetics and Genomic Sciences, Department of Artificial Intelligence and Human Health, Center for Transformative Disease Modeling, Tisch Cancer Institute, Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
bioRxiv : the preprint server for biology
|November 28, 2024
概括
研究人员确定了主蛋白丰度调节器 (MaPRs),可以在转录后控制基因表达. 这些关键调节剂对癌症生物学至关重要,并提供潜在的治疗点.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 蛋白质组学是指蛋白质组学.
- 癌症生物学 癌症生物学
背景情况:
- 蛋白质丰富度与mRNA水平的相关性只有适度.
- 通过核糖体,RNA结合蛋白 (RBPs) 的转录后调节,蛋白质体调节蛋白质水平.
- 了解这些调节网络对于破译基因表达和癌症发展至关重要.
研究的目的:
- 在十种癌症类型中识别主蛋白丰度调节器 (MaPRs).
- 分析MaPRs在转录后监管网络中的作用和癌症特异性漏洞.
- 通过实验证据验证发现.
主要方法:
- 开发一个计算管道,共同分析来自1305个瘤样本的转录组和蛋白质组.
- 基于网络连接,遗传依赖和RBPs的丰富性来识别MaPRs.
- 整合瘤上调,药物可用性和目标网络分析.
- 使用eCLIP结合和敲击测试进行验证.
主要成果:
- 确定了232到1394个每种癌症类型的MaPRs,介导高达79%的转录后调节网络.
- MaPRs表现出高的网络连接性,癌细胞的遗传依赖性,并为RBPs进行丰富.
- 通过结合瘤上调,药物可用性和网络分析,发现了癌症特异性漏洞.
- MaPRs比其他蛋白质更准确地预测瘤蛋白质亚型.
- 通过实验证据验证了RBP MaPR-目标关系.
结论:
- MaPRs是管理人类蛋白质组调节后转录网络的中央调节器.
- 这些发现突出了蛋白质组调节的基础上的多样化过程,并确定了癌症生物学中的关键调节者.
- MaPRs代表了癌症治疗的潜在治疗点.
相关概念视频
mTOR Signaling and Cancer Progression
3.7K
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...
3.7K
Abnormal Proliferation
4.5K
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...
4.5K
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
Negative Regulator Molecules
35.2K
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.
35.2K
Regulation of Expression at Multiple Steps
872
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
872
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


