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Chemoproteomic profiling by a bioorthogonal probe reveals cell growth inhibition by histone H4 dopaminylation

ABSTRACT: Dopaminylation, the covalent attachment of dopamine to the side chain of glutamine (Gln, Q) in proteins, represents a newly characterized class of posttranslational modifications. Due to the limited identification of substrates, the functions and molecular mechanisms associated with dopaminylation remain largely uncharacterized. Utilizing an alkyne-functionalized dopamine probe, we developed a method for selectively enriching dopaminylated proteins in whole-live-cell systems. This approach identified 4,133 putative dopamine-modified proteins and validated the dopaminylation of histone H4 at glutamine 27 (H4Q27dop). Functionally, H4Q27dop primarily exerts transcriptional repression in neuroblastoma cells and inhibits cell proliferation by downregulating the transcription of the cyclin D1 gene (CCND1), a well-known regulator of cell cycle progression. Our findings offer a valuable resource of dopaminylated substrate proteins and reveal a novel mechanism through which dopamine regulates cell growth in a neuroblastoma model.

ORGANISM(S): Homo Sapiens

SUBMITTER: Xi Mo

PROVIDER: PXD062963 | iProX | Fri Oct 24 00:00:00 GMT+01:00 2025

REPOSITORIES: iProX

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Chemoproteomic profiling by a bioorthogonal probe reveals cell growth inhibition by histone H4 dopaminylation

Project description:Dopaminylation, the covalent attachment of dopamine to the side chain of glutamine (Gln, Q) in proteins, has been identified as a class of posttranslational modification. Due to the limited number of substrates, the functions and underlying molecular mechanisms of dopaminylation are not fully characterized. Utilizing an alkyne-functionalized dopamine probe, we have developed a method to selectively enrich dopaminylated proteins in the whole-cell context. We identified 4133 proteins potentially modified with dopamine and validated the modification of histone H4 glutamine 27 by dopamine (H4Q27dop). H4Q27dop can inhibit cell proliferation through downregulating cyclin D1 gene CCND1 transcription, a classical well-known proliferation promoter. Our study provides a valuable resource of putative substrate proteins modified with dopamine and reveals a novel mechanism of dopamine regulating cell growth in a neuroblastoma cancer model.

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Chemoproteomic profiling by a bioorthogonal probe reveals cell growth inhibition by histone H4 dopaminylation

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