Non-histone lysine lactylation: Emerging roles in tumor biology and therapeutic implications

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2025-08-17 DOI:10.1016/j.arr.2025.102875

Qu Zhang , Bo Luo , Xinchen Sun , Hiroaki Nagashima , Yemei Wu , Gai Liang , Yan Luo , Ryohei Sasaki , Qin Qin

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Abstract

Lactate, a byproduct of glycolysis, was first identified to induce a novel post-translational modification (PTM) known as lysine lactylation (Kla) in 2019. Kla has been shown to regulate various biological processes, including transcription, metabolism, cell proliferation, and inflammatory responses, which are pivotal in both tumorigenesis and cellular aging. Initially, Kla was identified as an epigenetic marker on histones, where it regulates gene transcription. However, more recent studies have demonstrated widespread Kla modifications on non-histone proteins, suggesting their involvement in multiple tumorigenic processes, which are often dysregulated during aging. Unlike histone Kla, which influences gene accessibility and transcription, non-histone protein Kla exerts a more direct influence on protein levels and functions by modifying their stability, activity, or localization. This review summarizes the latest advances in non-histone Kla research, highlighting its regulatory factors and role in tumor biology and treatment resistance. Additionally, we discuss the potential implications of non-histone Kla in tumor diagnosis, prognosis, and targeted therapy.

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非组蛋白赖氨酸乳酸化：在肿瘤生物学和治疗意义中的新作用。

乳酸是糖酵解的副产物，于2019年首次被发现可诱导一种称为赖氨酸乳酸化（Kla）的新型翻译后修饰（PTM）。Kla已被证明调节多种生物过程，包括转录、代谢、细胞增殖和炎症反应，这在肿瘤发生和细胞衰老中都是关键。最初，Kla被确定为组蛋白上的表观遗传标记，在那里它调节基因转录。然而，最近的研究表明，Kla修饰在非组蛋白上广泛存在，表明它们参与多种致瘤过程，这些过程通常在衰老过程中失调。与影响基因可及性和转录的组蛋白Kla不同，非组蛋白Kla通过改变蛋白质的稳定性、活性或定位，对蛋白质水平和功能施加更直接的影响。本文综述了非组蛋白Kla的最新研究进展，重点介绍了非组蛋白Kla的调控因子及其在肿瘤生物学和治疗耐药中的作用。此外，我们还讨论了非组蛋白Kla在肿瘤诊断、预后和靶向治疗中的潜在意义。

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

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.