Department of Cancer Biology, Sols-Morreale Biomedical Research Institute (IIBM), Spanish National Research Council (CSIC), Universidad Autónoma de Madrid (UAM), Madrid, Spain.
ABC-RI, Algarve Biomedical Center Research Institute, Algarve Biomedical Center, Faro, Portugal.
Methods Mol Biol. 2025;2871:1-8. doi: 10.1007/978-1-0716-4217-7_1.
Forkhead box O (FOXO) transcription factors constitute a mammalian family of proteins, comprising FOXO1, FOXO3, FOXO4, and FOXO6. Originally recognized as downstream regulators within the insulin pathway, FOXO factors exhibit the ability to bind to diverse target gene promoters, thereby governing crucial facets of cellular homeostasis. These encompass cellular energy generation, resilience against oxidative stress, and the modulation of cell viability and proliferation. The dysregulation of FOXO proteins has been established as pivotal in metabolic disorders, human longevity, and the inhibition of tumorigenesis. Notably subject to posttranslational modifications for regulation, FOXO inactivation predominantly arises from excessive activation of their upstream modifying enzymes, presenting a plethora of potential avenues for pharmaceutical reinstatement of FOXO activity.
叉头框蛋白 O（FOXO）转录因子构成了哺乳动物蛋白家族，包括 FOXO1、FOXO3、FOXO4 和 FOXO6。最初被认为是胰岛素通路中的下游调节因子，FOXO 因子表现出与多种靶基因启动子结合的能力，从而调节细胞内稳态的关键方面。这些方面包括细胞能量产生、对氧化应激的抵抗力以及细胞活力和增殖的调节。FOXO 蛋白的失调已被确定在代谢紊乱、人类长寿和抑制肿瘤发生中起着关键作用。FOXO 的失活主要是由于其上游修饰酶的过度激活，这为药物恢复 FOXO 活性提供了多种潜在途径。
