Jialin Liang, Yuxin Xie, Danyan Su, Yusheng Pang
irst Affiliated Hospital of Guangxi Medical University. Guangxi University of Chinese Medicine.
China
Molecular Biology Reports
Mol Biol Rep 2026; 53:
DOI: 10.1007/s11033-026-12478-3
Abstract
Pulmonary arterial hypertension (PAH) is a complex vascular disease characterized by endothelial dysfunction, pulmonary arterial smooth muscle cell (PASMC) hyperproliferation, metabolic reprogramming, and immune-inflammatory remodeling. These pathological features are not fully explained by isolated signaling abnormalities and increasingly point to post-translational modification (PTM) crosstalk as an important layer of protein regulation. In this review, we examine the interplay among phosphorylation, ubiquitination, and SUMOylation, with a focus on how these PTMs influence protein stability, subcellular localization, and degradation in the PAH microenvironment. To distinguish disease-supported mechanisms from broader biological extrapolation, we apply a tiered evidence framework that separates crosstalk axes validated in human PAH or relevant experimental pulmonary hypertension models from those inferred from hypoxia- or cancer-related systems. Across these studies, several recurring patterns emerge, including phosphodegron-dependent substrate recognition, PTM-dependent enzyme recruitment, and context-specific coupling between SUMOylation and ubiquitin-mediated turnover. These mechanisms help explain how PTM dysregulation may weaken vasculoprotective signaling, including BMPR2-related pathways, while sustaining proliferative, inflammatory, and hypoxia-responsive signaling programs. We also discuss a conceptual systems-level model in which chronic stress reshapes the effective PTM enzyme pool through changes in enzyme abundance, substrate allocation, and subcellular compartmentalization. Finally, we consider the translational implications of targeting PTM crosstalk, including opportunities for selective intervention and current barriers related to network redundancy, off-target toxicity, and drug delivery.
Category
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Review Articles Concerning Pulmonary Vascular Disease
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
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