Introduction Post-translational modifications are fundamental regulators of gene expression, chromatin organization and cellular behavior. Dopaminylation, a recently identified modification involving covalent attachment of dopamine to glutamine residues on proteins, has emerged as a novel signaling mechanism, although its biologic functions and substrate landscape remain poorly understood.
Introduction
Post-translational modifications are fundamental regulators of gene expression, chromatin organization and cellular behavior. Dopaminylation, a recently identified modification involving covalent attachment of dopamine to glutamine residues on proteins, has emerged as a novel signaling mechanism, although its biologic functions and substrate landscape remain poorly understood.
Problem Statement
The absence of robust methods to comprehensively identify dopaminylated proteins has limited understanding of how dopamine-mediated protein modification influences transcriptional regulation and cancer biology. Whether dopaminylation participates directly in epigenetic control mechanisms and tumor growth regulation has remained largely unknown.
Summary
This study introduces a chemoproteomic platform capable of systematically identifying dopaminylated proteins and substantially expands the known dopaminylation landscape. Using an alkyne-functionalized dopamine probe, the investigators identified more than a thousand putative dopaminylated proteins and characterized histone H4 dopaminylation at glutamine 27 as a previously unrecognized epigenetic modification. Functional analyses demonstrated that H4Q27 dopaminylation acts as a transcriptional repressor in neuroblastoma cells by inhibiting binding of the transcription factor CEBPD at the CCND1 promoter, leading to cyclin D1 suppression and reduced cellular proliferation. These findings establish a direct mechanistic link between dopamine-associated protein modification and chromatin-mediated control of tumor growth. Importantly, the work extends the biologic significance of dopamine beyond neurotransmission and suggests that dopaminylation may represent a broader regulatory system influencing transcriptional programs, cell-cycle progression and oncogenesis. The large-scale substrate dataset generated in this study also provides a major resource for future exploration of dopamine-mediated signaling across multiple physiologic and disease contexts. Overall, this research identifies dopaminylation as an emerging epigenetic mechanism with potential implications for cancer biology and future therapeutic targeting.
Introduction: Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary liver cancer with poor prognosis and limited treatment options. While ICC has traditionally been considered a malignancy of biliary epithelial cells, increasing evidence suggests that hepatocytes can...
Introduction: Liver fibrosis is the key determinant of long-term outcomes in metabolic dysfunction-associated steatohepatitis (MASH). Activated hepatic stellate cells (HSCs) drive fibrogenesis, but effective antifibrotic therapies remain unavailable. This study investigated whether blocking the succinate–GPR91...
Introduction: The progression from metabolic dysfunction-associated fatty liver (MAFL) to metabolic dysfunction-associated steatohepatitis (MASH) is driven by complex interactions between hepatocytes and immune cells. This study identifies a novel spatial mechanism in the periportal (PP)...
Introduction: Cardiovascular–Kidney–Metabolic (CKM) syndrome recognizes the close interaction between obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. This review highlights the emerging role of the gut microbiome, particularly butyrate-producing bacteria, as a central...
• Small intestinal adenocarcinoma (SIA) is a rare gastrointestinal cancer with limited disease-specific prognostic biomarkers and generally poor outcomes. • This nationwide Dutch population-based study evaluated whether three routinely available immunohistochemical markers—CK7, CK20, and CDX2—have...
Introduction: Metabolic dysfunction–associated steatotic liver disease (MASLD) is closely linked to insulin resistance and type 2 diabetes, with the liver traditionally viewed as a key regulator of blood glucose through hepatic glucose production. However, emerging...
We are pioneers in clinical intelligence, dedicated to helping gastroenterologists harness the power of artificial intelligence to drive precision, efficiency, and patient growth.