Department of Liver Surgery, Hepatobiliary Pancreatic Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 5100080, China.
Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 5100080, China.
Cell Death Dis. 2022 Jul 25;13(7):646. doi: 10.1038/s41419-022-05081-4.
As a substrate and major effector of the mammalian target of rapamycin complex 1 (mTORC1), the biological functions of ribosomal protein S6 kinase (S6K) have been canonically assigned for cell size control by facilitating mRNA transcription, splicing, and protein synthesis. However, accumulating evidence implies that diverse stimuli and upstream regulators modulate S6K kinase activity, leading to the activation of a plethora of downstream substrates for distinct pathobiological functions. Beyond controlling cell size, S6K simultaneously plays crucial roles in directing cell apoptosis, metabolism, and feedback regulation of its upstream signals. Thus, we comprehensively summarize the emerging upstream regulators, downstream substrates, mouse models, clinical relevance, and candidate inhibitors for S6K and shed light on S6K as a potential therapeutic target for cancers.
作为哺乳动物雷帕霉素靶蛋白复合物 1（mTORC1）的底物和主要效应物，核糖体蛋白 S6 激酶（S6K）的生物学功能通过促进 mRNA 转录、剪接和蛋白质合成，被规范地分配用于细胞大小控制。然而，越来越多的证据表明，各种刺激和上游调节剂调节 S6K 激酶活性，导致其下游众多底物的激活，从而发挥不同的病理生物学功能。除了控制细胞大小外，S6K 还同时在指导细胞凋亡、代谢以及其上游信号的反馈调节中发挥关键作用。因此，我们全面总结了 S6K 的新兴上游调节剂、下游底物、小鼠模型、临床相关性和候选抑制剂，并探讨了 S6K 作为癌症潜在治疗靶点的可能性。
