Conjoint analysis of succinylome and phosphorylome reveals imbalanced HDAC phosphorylation-driven succinylation dynamic contributes to lung cancer

Sep 21, 2026

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Cancerous genetic mutations create complex post-translational modification (PTM) dynamics, where protein succinylation is known to reprogram cell metabolism and support malignant evolution. Regulatory interactions between succinylation and other PTMs within the PTM network remain poorly understood. A conjoint analysis and systematic clustering approach was applied to succinylome and phosphorylome from eight lung cancer patients, revealing coordinated intermodification patterns in both parallel and series.

LanguageEnglish

CategoryResearch & Report

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Abstract

Introduction

Materials and methods

Clinical sample collection and preparation

Briefings in Bioinformatics, 2024, 25(5), bbae415 [https://doi.org/10.1093/bib/bbae415](https://doi.org/10.1093/bib/bbae415) Case Study Conjoint analysis of succinylome and phosphorylome reveals imbalanced HDAC phosphorylation-driven succinylayion dynamic contibutes to lung cancer Yifan Guo 1 ,‡, Haoyu Wen1 ,‡, Zongwei Chen1 ,‡, Mengxia Jiao2 , Yuchen Zhang1 , Di Ge1 , Ronghua Liu2 , *, Jie Gu1 , * 1 Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China 2 Shanghai Fifth People’s Hospital and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, 131 Dongan Road, Shanghai 200032, China *Corresponding authors. Jie Gu, Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. E-mail: [gu.jie3@zs-hospital.sh.cn](gu.jie3@zs-hospital.sh.cn); Ronghua Liu, Shanghai Fifth People’s Hospital and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. E-mail [ronghualiu@fudan.edu.cn](ronghualiu@fudan.edu.cn) ‡Yifan Guo, Haoyu Wen, and Zongwei Chen contributed equally to this work. Abstract Cancerous genetic mutations result in a complex and comprehensive post-translational modification (PTM) dynamics, in which proteinsuccinylation 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. Received: April 16, 2024 . Revised: July 17, 2024 © The Author(s) 2024 . Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by-nc/4.0/](licenses/by-nc/4.0/)), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please [contact journals.permissions@oup.com](contact journals.permissions@oup.com) Graphical Abstract Keywords: succinylation; phosphorylation; lung cancer; proteome; metabolism Introduction Post-translational modifications (PTMs) change the properties of a protein by adding a modifying chemical group or another protein to one or more amino acid residues [1] . They contribute to the functional diversity of the proteome without forming new proteins or changing their abundance by covalently adding functional groups that can alter their charge, structure, and interactions [2] . They provide an efficient and rapid biological regulatory mechanism that flexibly regulates tumor proliferation and progression during tumor development [3] . Cancerous genetic mutations result in a relatively complex and comprehensive PTM grid that enriches the protein function of the tumor during its progression [4 , 5] . Recent studies have increasingly focused on the mechanism of tandem interference be

FAQs

What approach was used to study succinylome and phosphorylome in lung cancer?

The study used a conjoint analysis combined with a systematic clustering method to explore intermodification communications between succinylation and phosphorylation across samples.

What intermodification relationships were identified between succinylation and phosphorylation?

Intermodification cooperation was found in both parallel and series patterns within the PTM network.

How is HDAC phosphorylation linked to succinylation in lung cancer?

Phosphorylated activation of histone deacetylase (HDAC) favored succinylation of mitochondrial proteins by promoting removal of acetylation, supporting tandem regulation between phosphorylation and succinylation.

Sep 21, 2026

Uploaded by Asher