Yang Zeng Quan, Campeanu Ion John, Lopez Ivan, Syed Manaal, Jiang Yuanyuan, Afisllari Hilda
Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA.
Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Cells. 2025 Jun 7;14(12):863. doi: 10.3390/cells14120863.
NAA10 (N-alpha-acetyltransferase 10) is a pivotal enzyme in eukaryotic cells, serving as the catalytic subunit of the NatA complex, which is responsible for the N-terminal acetylation of approximately 40-50% of the human proteome. Beyond its canonical role in co-translational N-terminal acetylation, NAA10 also acetylates internal lysine residues of various proteins and exerts non-catalytic regulatory functions through diverse protein-protein interactions. Pathogenic variants in are linked to a spectrum of developmental disorders, most notably Ogden syndrome, which is characterized by neurodevelopmental delay, cardiac defects, and craniofacial anomalies. In cancer, NAA10 is frequently overexpressed or genomically amplified, where its dysregulation correlates with tumor aggressiveness and poor prognosis. Functional studies implicate NAA10 in regulating cell cycle progression, apoptosis, migration, and other hallmarks of cancer. In this review, we summarize the structure, molecular mechanisms, and physiological functions of NAA10, as well as its roles in human diseases and cancer. We present in silico pan-cancer analyses that highlight its clinical significance and potential downstream pathways. Furthermore, we discuss the therapeutic potential and challenges of targeting NAA10 in cancer, and propose future research directions to better understand its multifaceted roles in health and disease.
NAA10（N-α-乙酰基转移酶10）是真核细胞中的一种关键酶，作为NatA复合物的催化亚基，负责约40-50%的人类蛋白质组的N端乙酰化。除了在共翻译N端乙酰化中的经典作用外，NAA10还可乙酰化各种蛋白质的内部赖氨酸残基，并通过多种蛋白质-蛋白质相互作用发挥非催化调节功能。NAA10的致病变体与一系列发育障碍有关，最显著的是奥格登综合征，其特征为神经发育迟缓、心脏缺陷和颅面异常。在癌症中，NAA10经常过度表达或发生基因组扩增，其失调与肿瘤侵袭性和不良预后相关。功能研究表明NAA10参与调节细胞周期进程、细胞凋亡、迁移及癌症的其他特征。在本综述中，我们总结了NAA10的结构、分子机制和生理功能，及其在人类疾病和癌症中的作用。我们展示了突出其临床意义和潜在下游途径的全癌生物信息学分析。此外，我们讨论了针对癌症中NAA10进行靶向治疗的潜力和挑战，并提出了未来的研究方向，以更好地理解其在健康和疾病中的多方面作用。
