Chemically mediated 14-3-3 protein post-translational modification interference: design of molecular glue and the application in cancer treatment
10.16438/j.0513-4870.2024-0418
- VernacularTitle:化学介导的14-3-3蛋白翻译后修饰干预: 分子胶设计及其在肿瘤治疗中的应用
- Author:
Liu-yi WU
;
Long-jing LI
;
Yu-cheng TIAN
;
Qian-qian XU
;
Wei WEI
;
Zhi-yu LI
;
Jin-lei BIAN
- Publication Type:Research Article
- Keywords:
14-3-3 molecular glue;
protein-protein interaction;
RAF proto-oncogene serine/threonine-protein kinase;
estrogen receptor α;
p53
- From:
Acta Pharmaceutica Sinica
2024;59(11):2953-2961
- CountryChina
- Language:Chinese
-
Abstract:
Protein-protein interactions (PPIs) are not only crucial for the assembly of protein complexes but also fundamental for maintaining normal biological functions. These interactions are vital for protein structure and biological functionality and play a central role in cellular signaling, metabolic pathways, and regulatory networks. The 14-3-3 protein, highly conserved and widely expressed in eukaryotes, primarily recognizes and binds to its partner proteins to participate in essential life processes such as cell cycle control, signal transduction, and energy metabolism. This review discusses the role of dysregulated PPIs between 14-3-3 proteins and their partner proteins such as estrogen receptor α (estrogen receptor α, ERα), RAF proto-oncogene serine/threonine-protein kinase (C-RAF/RAF-1), and p53 in the onset and progression of tumors, focusing on the research progress of 14-3-3/ERα, 14-3-3/C-RAF, and 14-3-3/p53 molecular glues. These molecular glues, by mimicking or enhancing the phosphorylation sites of serine on partner proteins, form covalent bonds, salt bridges, and hydrogen bonds with 14-3-3 proteins, thereby enhancing the stability of PPIs and effectively intervening in protein activity and signaling under pathological conditions. Additionally, this article explores the potential of this chemical intervention strategy in clinically suppressing tumor progression, providing a theoretical foundation and practical guidance for future research directions.
