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Review
. 2025 Sep 11;68(1):86.
doi: 10.1007/s12016-025-09081-y.

The Ubiquitin-Proteasome System in Asthma: Mechanisms and Therapeutic Possibilities

Shuangyu He #  1 , Siqi Wen #  1 , Zhen Wang  2 , Yonggang Qu  2 , Chongyu Xu  1 , Danni Li  3 , Jiapeng Hu  4
Affiliations
Review

The Ubiquitin-Proteasome System in Asthma: Mechanisms and Therapeutic Possibilities

Shuangyu He et al. Clin Rev Allergy Immunol. .

Abstract

The ubiquitin-proteasome system (UPS) plays a crucial role in asthma by regulating protein stability And activity through post-translational modifications. This review provides a comprehensive Analysis of 42 UPS components in asthma, including one E2 ubiquitin-conjugating enzyme, 27 E3 ubiquitin ligases, eight deubiquitinating enzymes (DUBs), one dual-function (both E3 and DUB) enzyme, And five components of the 26S proteasome. Our Analysis focuses on four key pathological features, including airway inflammation, hyperresponsiveness, mucus hypersecretion, And remodeling. We identify 25 E3 ligase-substrate pairs and seven DUB-substrate pairs, detailing their ubiquitination and deubiquitination mechanisms. Additionally, a Literature review combined with GWAS data reveals 20 single-nucleotide polymorphisms (SNPs) across nine UPS Genes associated with asthma susceptibility. Therapeutic evaluations highlight 24 druggable UPS targets. Furthermore, we underscore 24 UPS-related compounds, with ten having established relevance to asthma And 14 exhibiting untapped potential. Emerging treatment strategies such as PROTACs and nanovaccines show promising potential. Overall, these findings provide new insights into UPS-mediated mechanisms and genetics in asthma and highlight its potential as a therapeutic target, paving the way for future research and clinical applications.

Keywords: Asthma; SNP; Therapeutic targeting; Ubiquitin–proteasome system.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

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