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

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Abstract

S6K1 (ribosomal protein S6 kinase beta-1) is a critical serine/threonine kinase involved in the regulation of various cellular processes, including protein synthesis, gene expression, and metabolic homeostasis. The structural complexity of S6K1, with its multiple isoforms and unique kinase domain, allows for diverse functionality across different cellular contexts. In this review, we report the intricate structure of S6K1, highlighting the significance of its kinase domain. Additionally, we explored the tissue-specific expression and subcellular localization of S6K1 isoforms, emphasizing their distinct roles in cellular processes. The regulation of S6K1 extends beyond transcriptional control, with post-translational modifications such as phosphorylation and acetylation playing crucial roles in its activity and stability. The physiological implications of S6K1 are vast, influencing processes from cell growth and protein synthesis to immune responses and muscle hypertrophy. However, dysregulation of S6K1 is implicated in numerous pathological conditions, including cancer Studies reveal that altered S6K1 activity, particularly in its phosphorylation state, can lead to reduced neuronal viability, contributing to the progression of diseases such as Parkinson's. This manuscript synthesizes current knowledge on S6K1, offering insights into its multifaceted roles and highlighting its potential as a therapeutic target in various disease contexts.

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