Khalil Mahmoud I, Helal Mohamed, El-Sayed Ahmed F, El Hajj Rana, Holail Jasmine, Houssein Marwa, Waraky Ahmed, Pardo Olivier E
Department of Biological Sciences, Faculty of Sciences, Beirut Arab University, Beirut P.O. Box 11-5020, Lebanon.
Molecular Biology Unit, Department of Zoology, Faculty of Science, Alexandria University, Alexandria 21568, Egypt.
Int J Mol Sci. 2024 Dec 28;26(1):176. doi: 10.3390/ijms26010176.
S6 Kinase 2 (S6K2) is a key regulator of cellular signaling and is crucial for cell growth, proliferation, and survival. This review is divided into two parts: the first focuses on the complex network of upstream effectors, downstream modulators, and post-translational modifications (PTMs) that regulate S6K2 activity. We emphasize the dynamic nature of S6K2 regulation, highlighting its critical role in cellular homeostasis and its potential as a therapeutic target in diseases like cancer. The second part utilizes in silico analyses, employing computational tools to model S6K2's three-dimensional structure and predict its interaction networks. Molecular dynamics simulations and docking studies reveal potential binding sites and interactions with novel known inhibitors. We also examine the effects of environmental contaminants that potentially disrupt S6K2 function and provide insights into the role of external factors that could impact its regulatory mechanisms. These computational findings provide a deeper understanding of the conformational dynamics of S6K2 and its interactions with its inhibitors. Together, this integrated biochemical and computational approach enhances our understanding of S6K2 regulation and identifies potential new therapeutic strategies targeting S6K2 in the oncology setting.
核糖体蛋白S6激酶2（S6K2）是细胞信号传导的关键调节因子，对细胞生长、增殖和存活至关重要。本综述分为两部分：第一部分聚焦于调节S6K2活性的上游效应物、下游调节剂和翻译后修饰（PTM）的复杂网络。我们强调S6K2调节的动态性质，突出其在细胞稳态中的关键作用及其作为癌症等疾病治疗靶点的潜力。第二部分利用计算机分析，使用计算工具对S6K2的三维结构进行建模并预测其相互作用网络。分子动力学模拟和对接研究揭示了潜在的结合位点以及与新型已知抑制剂的相互作用。我们还研究了可能破坏S6K2功能的环境污染物的影响，并深入了解可能影响其调节机制的外部因素的作用。这些计算结果为S6K2的构象动力学及其与抑制剂的相互作用提供了更深入的理解。总之，这种综合的生化和计算方法增强了我们对S6K2调节的理解，并确定了在肿瘤学环境中靶向S6K2的潜在新治疗策略。
