联合分析琥珀酸酯和磷酸化团揭示了HDAC磷酸化驱动的琥珀酸酯动态对肺癌的不平衡
Conjoint analysis of succinylome and phosphorylome reveals imbalanced HDAC phosphorylation-driven succinylayion dynamic contibutes to lung cancer
影响因子:7.70000
分区:生物学2区 / 数学与计算生物学1区 生化研究方法2区
发表日期:2024 Jul 25
作者:
Yifan Guo, Haoyu Wen, Zongwei Chen, Mengxia Jiao, Yuchen Zhang, Di Ge, Ronghua Liu, Jie Gu
摘要
癌性遗传突变导致复杂而全面的翻译后修饰（PTM）动力学，其中蛋白琥珀酰化以其重新编程细胞代谢的能力而闻名，并参与恶性进化。关于PTM网络中琥珀酰化与其他PTM之间的调节相互作用知之甚少。在这里，我们开发了一种联合分析和系统的聚类方法，以探索来自八名肺癌患者的琥珀酸酯和磷酸化体之间的变化通信。我们发现平行和串联的互化均匀度。除了直接参与新陈代谢途径外，线粒体中的一些磷脂被确定为一种上游调节性修饰，指导癌症代谢重编程中的琥珀体组动力学。组蛋白脱乙酰基酶（HDAC）在肺癌中的磷酸化活化导致去除乙酰化，并有利于发生琥珀酰化修饰线粒体蛋白的发生。这些结果表明，PTM网络中的琥珀酸化和磷酸化之间的串联调节，并提供了与HDAC相关的靶标，以介入线粒体琥珀酰化和癌症代谢重编程。
Abstract
Cancerous genetic mutations result in a complex and comprehensive post-translational modification (PTM) dynamics, in which protein succinylation is well known for its ability to reprogram cell metabolism and is involved in the malignant evolution. Little is known about the regulatory interactions between succinylation and other PTMs in the PTM network. Here, we developed a conjoint analysis and systematic clustering method to explore the intermodification communications between succinylome and phosphorylome from eight lung cancer patients. We found that the intermodification coorperation in both parallel and series. Besides directly participating in metabolism pathways, some phosphosites out of mitochondria were identified as an upstream regulatory modification directing succinylome dynamics in cancer metabolism reprogramming. Phosphorylated activation of histone deacetylase (HDAC) in lung cancer resulted in the removal of acetylation and favored the occurrence of succinylation modification of mitochondrial proteins. These results suggest a tandem regulation between succinylation and phosphorylation in the PTM network and provide HDAC-related targets for intervening mitochondrial succinylation and cancer metabolism reprogramming.