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<p>Dopaminylation, the covalent attachment of dopamine to the side chain of glutamine in proteins, represents a newly characterized class of posttranslational modifications. Because of the limited identification of substrates, the functions and molecular mechanisms associated with dopaminylation remain largely uncharacterized. Using an alkyne-functionalized dopamine probe, we developed a method for selectively enriching dopaminylated proteins in whole-cell systems. This approach provided a comprehensive resource of 4,133 dopamine-enriched protein candidates and peptide-level analysis with acid-cleavable tags identified 1,181 putative dopaminylated proteins, including histone H4 dopaminylation at Q27 (H4Q27dop), which we further validated. Functionally, H4Q27dop acts as a transcriptional repressor in a neuroblastoma model, where it blocks CEBPD binding at the <i>CCND1</i> promoter, leading to transcriptional downregulation of <i>CCND1</i> and subsequent suppression of cell proliferation. Our findings provide both a valuable resource of dopaminylated substrate proteins and a distinct mechanistic insight into how dopamine regulates neuroblastoma cell growth.</p><p></p>

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Chemoproteomic profiling reveals histone H4 dopaminylation inhibiting cell growth

  • 期刊论文

  • 发表日期：

    2026年5月8日

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  • Yinfeng Zhang,
  • Yaqi Yang,
  • Wenyan Wu,
  • Min Zhang,
  • Jianan Rao,
  • Wenting Song,
  • Yi Pan,
  • Nan Shen,
  • Linxue Li,
  • Taishan Min,
  • Kai Li,
  • Xiaoqing Zhang,
  • Xin-Yue Qiu,
  • Shu-Yu Zhang,
  • Wenjun Yang,
  • Jianye Zang,
  • Yu Liu,
  • Xi Mo

摘要

Dopaminylation, the covalent attachment of dopamine to the side chain of glutamine in proteins, represents a newly characterized class of posttranslational modifications. Because of the limited identification of substrates, the functions and molecular mechanisms associated with dopaminylation remain largely uncharacterized. Using an alkyne-functionalized dopamine probe, we developed a method for selectively enriching dopaminylated proteins in whole-cell systems. This approach provided a comprehensive resource of 4,133 dopamine-enriched protein candidates and peptide-level analysis with acid-cleavable tags identified 1,181 putative dopaminylated proteins, including histone H4 dopaminylation at Q27 (H4Q27dop), which we further validated. Functionally, H4Q27dop acts as a transcriptional repressor in a neuroblastoma model, where it blocks CEBPD binding at the CCND1 promoter, leading to transcriptional downregulation of CCND1 and subsequent suppression of cell proliferation. Our findings provide both a valuable resource of dopaminylated substrate proteins and a distinct mechanistic insight into how dopamine regulates neuroblastoma cell growth.