CDK13：从生物学功能到相关疾病及治疗靶向策略

CDK13: From biological function to associated diseases and therapeutic targeting strategies

摘要

细胞周期依赖性激酶13（CDK13）是细胞周期依赖性激酶家族的重要一员，在与细胞周期蛋白K（Cyclin K）结合并发挥其对基因转录、RNA选择性剪接以及蛋白质翻译等重要生理过程中起着重要的生物学功能作用。尽管CDK13和其同源物细胞周期依赖性激酶12（CDK12）具有相似氨基酸序列，但是它们在表达模式、调控机制及功能方面却表现出截然不同的特点。近年来发现，CDK13不仅是一些罕见病的致病因素，而且在参与不同类型的癌症发生发展中，既可以作为癌基因，也可以作为抑癌基因存在，甚至可以通过改变相关信号通路调节肿瘤微环境。本文总结了CDK13的分子学性质、组织分布、主要生物学功能，提炼了CDK13在不同类型的肿瘤中发挥的作用及与一些罕见病的关系，最后列举了目前针对CDK12/13靶向药物的研发进展及其面临的问题，指出了当前研究中存在的重要问题，并对其未来的基础研究以及临床应用提出了一些推测性建议。

Abstract

Cyclin-dependent kinase 13 (CDK13), an important member of the cyclin-dependent kinase family, plays crucial biological roles in gene transcription, alternative RNA splicing, and protein translation upon binding to cyclin K. Although CDK13 and its homolog, cyclin-dependent kinase 12 (CDK12), share similar amino acid sequences, they exhibit distinct characteristics in expression patterns, regulatory mechanisms, and functions. Recent studies have revealed that CDK13 not only contributes to the pathogenesis of certain rare diseases but also participates in the development and progression of various types of cancer, acting either as an oncogene or a tumor suppressor, and even modulating the tumor microenvironment by altering relevant signaling pathways. This article summarizes the molecular properties, tissue distribution, and major biological functions of CDK13, highlights the roles of CDK13 in various types of tumors and its association with certain rare diseases, and finally reviews the current progress and challenges in the development of targeted therapies against CDK12/13. It also identifies key unresolved issues in current research and offers tentative suggestions for future basic research and clinical applications.

关键词

细胞周期依赖性激酶13 / 靶向治疗 / 干扰素基因刺激因子 / 先天性心脏缺陷、面部特征异常和智力发育障碍 / 细胞周期依赖性激酶12和13抑制剂

Key words

CDK13 / Targeted therapy / Stimulator of interferon genes / Congenital heart defects, dysmorphic facial features, and intellectual developmental disorder / CDK12/13 inhibitor

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基金资助

国家自然科学基金地区科学基金项目(82260536)

内蒙古自治区卫生健康科技项目(2025NMWJKJXM0192)