癌性基因突变会导致复杂而全面的翻译后修饰（PTM）动力学，其中蛋白质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。关于琥珀酰化与 PTM 网络中其他 PTM 之间的调控相互作用知之甚少。在这里，我们开发了一种联合分析和系统聚类方法来探索八名肺癌患者的琥珀酰组和磷酰组之间的相互修饰通讯。我们发现并联和串联都存在互变合作。除了直接参与代谢途径外，线粒体外的一些磷酸位点还被确定为在癌症代谢重编程中指导琥珀酰组动力学的上游调节修饰。肺癌中组蛋白脱乙酰酶（HDAC）的磷酸化激活导致乙酰化的去除，并有利于线粒体蛋白琥珀酰化修饰的发生。这些结果表明 PTM 网络中琥珀酰化和磷酸化之间存在串联调节，并为干预线粒体琥珀酰化和癌症代谢重编程提供了 HDAC 相关靶标。© 作者 2024。由牛津大学出版社出版。

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.© The Author(s) 2024. Published by Oxford University Press.