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Chemically mediated 14-3-3 protein post-translational modification interference: design of molecular glue and the application in cancer treatment
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Liu-yi WU, Long-jing LI, Yu-cheng TIAN, Qian-qian XU, Wei WEI, Zhi-yu LI, Jin-lei BIAN*
Acta Pharmaceutica Sinica | 2024, 59(11) : 2953 - 2961
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Acta Pharmaceutica Sinica | 2024, 59(11): 2953-2961
Chemically mediated 14-3-3 protein post-translational modification interference: design of molecular glue and the application in cancer treatment
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Liu-yi WU, Long-jing LI, Yu-cheng TIAN, Qian-qian XU, Wei WEI, Zhi-yu LI, Jin-lei BIAN*
Affiliations
  • School of Pharmacy, China Pharmaceutical University, Nanjing 211112, China
Published: 2024-11-12 doi: 10.16438/j.0513-4870.2024-0418
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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.

14-3-3 molecular glue  /  protein-protein interaction  /  RAF proto-oncogene serine/threonine-protein kinase  /  estrogen receptor α  /  p53
Liu-yi WU, Long-jing LI, Yu-cheng TIAN, Qian-qian XU, Wei WEI, Zhi-yu LI, Jin-lei BIAN. Chemically mediated 14-3-3 protein post-translational modification interference: design of molecular glue and the application in cancer treatment[J]. Acta Pharmaceutica Sinica, 2024 , 59 (11) : 2953 -2961 . DOI: 10.16438/j.0513-4870.2024-0418
Year 2024 volume 59 Issue 11
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doi: 10.16438/j.0513-4870.2024-0418
  • Receive Date:2024-04-30
  • Online Date:2025-11-24
  • Published:2024-11-12
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  • Received:2024-04-30
  • Revised:2024-08-15
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    School of Pharmacy, China Pharmaceutical University, Nanjing 211112, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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