欧核生物翻译启动因子4E的调节作为潜在的抗癌战略
Xintao Gao1, Yonglong Jin2, Wenyong Zhu3
1College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China.
Journal of medicinal chemistry
|September 19, 2023
概括
细胞转化启动因子4E (eIF4E) 对癌症生长至关重要. 针对eIF4E的战略,特别是与eIF4G的相互作用,为开发有效的抗癌药物提供了有希望的新途径.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 在癌症中,真核细胞转化启动因子 (eIFs) 的上调.
- eIF4E是癌细胞增殖的关键调节剂,也是潜在的治疗标.
- 目前的eIF4E向策略包括抑制合成,eIF4E/eIF4G相互作用,酸化和使用抑制剂.
研究的目的:
- 审查eIF4E的监管机制.
- 总结开发和发现eIF4E抑制剂策略的进展情况.
- 为eIF4E抑制剂设计提出新的策略.
主要方法:
- 对eIF4E监管机制的文献综述.
- 对当前和新兴eIF4E抑制剂策略的分析.
- 探索作为治疗目标的eIF4E/eIF4G相互作用.
主要成果:
- 有几种策略可以抑制eIF4E,但没有一个是临床批准的.
- 针对eIF4E的小分子抑制剂正在临床试验中.
- 与eIF4E/eIF4G相互作用的干扰是一个正在发展的领域.
结论:
- eIF4E在癌细胞生长中发挥着核心作用.
- 针对eIF4E是一个有前途的抗癌策略.
- 干扰eIF4E/eIF4G相互作用为设计eIF4E抑制剂提供了一种新且潜在的首选方法.
相关概念视频
Initiation of Translation
34.1K
Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
34.1K
Mitogens and the Cell Cycle
6.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.5K
Regulation of Expression Occurs at Multiple Steps
22.8K
Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
22.8K
Leaky Scanning
5.2K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.2K
mTOR Signaling and Cancer Progression
3.8K
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...
3.8K
Regulation of Expression at Multiple Steps
942
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...
942


