Therapeutic Potential of Translational Readthrough at Disease-Associated Premature Termination Codons From Tumor Suppressor Genes

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
IUBMB Life Pub Date : 2025-05-02 DOI:10.1002/iub.70018
Leire Torices, Caroline E. Nunes-Xavier, Rafael Pulido
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引用次数: 0

Abstract

Tumor suppressor genes are frequently targeted by mutations introducing premature termination codons (PTC) in the protein coding sequence, both in sporadic cancers and in the germline of patients with cancer predisposition syndromes. These mutations have a high pathogenic impact since they generate C-terminal truncated proteins with altered stability and function. In addition, PTC mutations trigger transcript degradation by nonsense-mediated mRNA decay. Suppression of PTC by translational readthrough restores protein biosynthesis and stabilizes the PTC-targeted mRNA, making a suitable therapeutic approach the reconstitution of active full-length tumor suppressor proteins by pharmacologically-induced translational readthrough. Here, we review the recent advances in small molecule pharmacological induction of translational readthrough of disease-associated PTC from tumor suppressor genes, and discuss the therapeutic potential of translational readthrough in specific groups of patients with hereditary syndromic cancers.

Abstract Image

肿瘤抑制基因中与疾病相关的过早终止密码子翻译读通的治疗潜力
在散发性癌症和癌症易感综合征患者的种系中,肿瘤抑制基因经常被在蛋白质编码序列中引入过早终止密码子(PTC)的突变靶向。这些突变具有高致病性,因为它们产生c端截断的蛋白质,其稳定性和功能发生改变。此外,PTC突变通过无义介导的mRNA衰变触发转录物降解。通过翻译读透抑制PTC恢复蛋白的生物合成,稳定PTC靶向mRNA,为药理学诱导的翻译读透重建活性全长肿瘤抑制蛋白提供了合适的治疗途径。在此,我们回顾了肿瘤抑制基因介导疾病相关PTC的小分子药理诱导的最新进展,并讨论了翻译读通在特定遗传综合征癌症患者群体中的治疗潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
IUBMB Life
IUBMB Life 生物-生化与分子生物学
CiteScore
10.60
自引率
0.00%
发文量
109
审稿时长
4-8 weeks
期刊介绍: IUBMB Life is the flagship journal of the International Union of Biochemistry and Molecular Biology and is devoted to the rapid publication of the most novel and significant original research articles, reviews, and hypotheses in the broadly defined fields of biochemistry, molecular biology, cell biology, and molecular medicine.
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