核定位信号标记系统:在当前治疗设计的背景下,相关的核导入原则
Ritabrita Goswami1, Aarohi Gupta1, Olga Bednova2
1Department of Chemistry, University of Massachusetts, Massachusetts, USA. rotello@chem.umass.edu.
Chemical Society reviews
|November 30, 2023
概括
通过使用核定位信号 (NLS) 将治疗药物向细胞核,可以提高药物的疗效并减少副作用. 本路线图指导NLS疗法的开发,以改善治疗结果.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 治疗药物的核向提高了疗效,并最大限度地减少了非向效应.
- 活跃的核运输和核孔复合体转移是核定位的关键.
- 核定位信号 (NLS) 图案对于核进口至关重要.
研究的目的:
- 为了解核进口机制提供一个路线图.
- 为了指导NLS治疗的可操作的治疗设计.
- 通过增强核定位来提高治疗疗效.
主要方法:
- 核进口机制的审查.
- 核定位信号 (NLS) 模式的分析.
- 治疗设计的路线图.
主要成果:
- 自2000年以来,基于NLS的系统取得了显著进展.
- 了解基本的核进口机制.
- 开发NLS疗法的框架.
结论:
- 核向是治疗开发的可行策略.
- NLS-疗法为改善治疗疗效提供了潜力.
- 进一步的研究可以优化基于NLS的药物输送.
更多相关视频
10:10Spatiotemporally Controlled Nuclear Translocation of Guests in Living Cells Using Caged Molecular Glues as Photoactivatable Tags
Published on: January 17, 2019
10.5K
10:04Radionuclide-fluorescence Reporter Gene Imaging to Track Tumor Progression in Rodent Tumor Models
Published on: March 13, 2018
12.1K
相关概念视频
Nuclear Localization Signals and Import
5.7K
Proteins targeted to the nucleus carry short stretches of amino acid sequences called the nuclear localization signal or NLS. Classical nuclear localization signals are of two types: monopartite and bipartite NLS. Monopartite classical NLS (cNLS) consists of a single cluster of 4-8 amino acids. Bipartite cNLS consists of two clusters of 2-3 amino acids and a 9-12 residue long proline-rich linker bridging the two clusters. Signal clusters are rich in positively charged amino acids such as...
5.7K
Nuclear Protein Sorting
4.6K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.6K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Nuclear Export
3.7K
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
3.7K
Directionality of Nuclear Transport
3.3K
Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
3.3K
Nuclear Export of mRNA
7.7K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.7K
