TF-PROTAC 能够对转录因子进行有针对性的降解
Jing Liu1, He Chen2, H Ümit Kaniskan2
1Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, United States.
Journal of the American Chemical Society
|June 8, 2021
概括
转录因子 (TF) 是不可抗药的目标,但TF-PROTAC提供了一个新的策略. 这些分子使用DNA选择性降解TFs, 显示癌症治疗的希望.
科学领域:
- 分子生物学
- 药物发现
- 生物化学
背景情况:
- 转录因子 (TF) 在癌症等人类疾病中至关重要,但在很大程度上是无法治疗的.
- 目前的治疗策略难以有效地针对大多数TF.
- 化向基因组 (PROTACs) 通过无素蛋白酶系统降解向蛋白质.
研究的目的:
- 开发一种新的平台,TF-PROTACs,用于选择性降解转录因子.
- 证明TF-PROTACs在降解特定TF的有效性及其治疗潜力.
主要方法:
- 开发一种TF-PROTAC平台,通过点击化学将DNA寡核酸与E3酶连接物连接起来.
- 针对NF-κB (p65) 和E2F1的基于VHL的TF-PROTAC的设计和合成
- 在细胞模型中验证TF降解和抗增殖作用.
主要成果:
- 在细胞中,TF- PROTACs成功地和选择性地降解了内源性p65和E2F1蛋白.
- 开发的TF-PROTACs (dNF-κB和dE2F) 显示出强大的抗增殖作用.
- DNA 寡核酸成分决定了TF 降解的特异性.
结论:
- TF-PROTAC代表了针对TF降解的可通用的平台.
- 这种方法提供了一种针对以前无法治疗的转录因子的通用策略.
- 对于开发新的癌症疗法,TF-PROTAC具有显著的潜力.
相关概念视频
General Transcription Factors
6.1K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
6.1K
Transcription Factors
79.8K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
79.8K
Transcription Attenuation in Prokaryotes
16.6K
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
16.6K
TGF - β Signaling Pathway
8.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
8.2K
Master Transcription Regulators
7.3K
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...
7.3K
Master Transcription Regulators
2.4K
2.4K


