酪蛋白激酶Ⅱ:衰老与衰老相关疾病调控  

Protein Kinase CK2:Regulation of Aging and Aging-related Diseases

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作  者:王瑞淇 杨杰良 王子梅 WANG Rui-Qi;YANG Jie-Liang;WANG Zi-Mei(Guangdong Key Laboratory of Genome Stability and Human Disease Prevention,Shenzhen 518055,Guangdong,China;Shenzhen Key Laboratory of Anti-aging and Regeneration,Carson International Cancer Center,Shenzhen University Medical School,Shenzhen 518055,Guangdong,China)

机构地区:[1]广东市基因组稳定性与人类疾病预防重点实验室,广东深圳518055 [2]深圳市抗衰老与再生重点实验室,深圳市卡尔森国际肿瘤重点实验室,深圳大学医学部基础医学院,广东深圳518055

出  处:《中国生物化学与分子生物学报》2025年第3期333-343,共11页Chinese Journal of Biochemistry and Molecular Biology

基  金:科技部重点研发计划(No.2023YFC25099002,2024YFA091872);国家自然科学基金项目(No.81971321);深圳市科技计划基础研究项目(No.JCYJ20210324094606017)资助。

摘  要:衰老是各种分子和细胞损伤随时间累积的结果,涉及3类共12种特征性标志,包括基因组不稳定性、端粒损耗、表观遗传改变、蛋白质稳态丧失、巨自噬失能等原发性标志;营养感应失调、线粒体功能障碍、细胞衰老等拮抗性标志,干细胞耗竭、细胞间通讯改变、慢性炎症和生态失调等综合性标志。因此,研究单一通路功能的细胞信号因子难以全面理解复杂的衰老机制。酪蛋白激酶Ⅱ(casein kinase 2,CK2)是最早被鉴定的蛋白质激酶之一,可以磷酸化数百种底物的丝/苏/酪氨酸位点,具有高度组成性表达活性,广泛参与细胞增殖、分化、凋亡、应激、代谢和免疫等功能调节,发挥着协同各类信号分子通路交叉整合的独特作用,对维持细胞存活和稳态具有重要意义。近年研究揭示,CK2在衰老过程中呈现表达水平及酶活性扰动现象,不同动物、组织器官及细胞模型存在一定异质性。总体而言,CK2的表达下调可促进衰老的原发性标志发展、但减轻衰老的拮抗性标志并改善衰老的综合标志,呈现双重效应和相互关联的机制特征。值得注意的是,多种衰老相关性疾病均伴随CK2表达及酶活性的异常激活,包括肿瘤、心血管疾病、慢性代谢性疾病、神经系统以及骨骼的退化性疾病等。因此,维持CK2稳态有望成为延缓衰老的有效策略。本文总结了CK2与衰老研究的最新进展,不仅有助于深入理解衰老与衰老相关性疾病的共性机制,而且为开发早期防治衰老相关性疾病的潜在药物靶点提供了理论依据。Aging is the result of the accumulation of various molecular and cellular damages over time,encompassing 12 characteristic hallmarks divided into three categories.These include primary hallmarks such as genomic instability,telomere attrition,epigenetic alterations,loss of proteostasis,and disabled macroautophagy;antagonistic hallmarks like deregulated nutrient sensing,mitochondrial dysfunction,and cellular senescence;and integrative hallmarks including stem cell exhaustion,altered intercellular communication,chronic inflammation and dysbiosis.Therefore,investigating cellular signaling factors within a single pathway is insufficient to comprehensively understand the complex mechanisms underlying aging.Casein kinase II(CK2),one of the earliest identified protein kinases,is capable of phosphorylating serine/threonine/tyrosine residues on hundreds of substrates.It exhibits highly constitutive expression and activity,and is extensively involved in the regulation of cellular processes such as proliferation,differentiation,apoptosis,stress response,metabolism,and immune function.CK2 plays a unique role in coordinating the cross-talk and integration of various signaling pathways,which is crucial for maintaining cell survival and homeostasis.Recent studies have revealed that CK2 exhibits perturbations in both expression levels and enzymatic activity during aging process,with notable heterogeneity observed across different animals,tissues and cellular models.Overall,the downregulation of CK2 expression not only promotes the development of primary hallmarks but also alleviates antagonistic hallmarks and ameliorates integrative hallmarks of aging,demonstrating dual effect and interconnected mechanisms.Notably,aberrant activation in CK2 expression and activity are associated with various aging-related diseases,including cancer,cardiovascular diseases,chronic metabolic disorders,neurodegenerative diseases and skeletal degenerative conditions.Therefore,maintaining CK2 homeostasis may represent an effective strategy for delaying

关 键 词:酪蛋白激酶2 衰老 细胞衰老 衰老相关性疾病 

分 类 号:Q5[生物学—生物化学]

 

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