The Multifaceted Role of S6K1 in Cellular Regulation and Disease: Structural Insights, Isoform-Specific Functions, and Therapeutic Potential

Abstract

S6K1 (ribosomal protein S6 kinase beta-1) is a serine/threonine kinase integral to regulating protein synthesis, gene expression, and metabolic homeostasis. Its structural complexity, including multiple isoforms and a unique kinase domain, enables diverse functions across cellular contexts. This review examines the intricate structure of S6K1, its tissue-specific expression, and subcellular localization, emphasizing distinct roles in cellular processes. Beyond transcriptional control, S6K1 activity and stability are critically influenced by post-translational modifications like phosphorylation and acetylation. S6K1’s physiological roles span cell growth, immune responses, and muscle hypertrophy, while its dysregulation is linked to cancer, cardiovascular diseases, metabolic disorders, and neurodegeneration. In neurodegenerative diseases, altered S6K1 activity, particularly its phosphorylation, is associated with reduced neuronal viability, contributing to conditions like Parkinson’s. This manuscript synthesizes current knowledge on S6K1, highlighting its therapeutic potential across various diseases.