Chemoproteomic profiling by a bioorthogonal probe reveals cell growth inhibition by histone H4 dopaminylation
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ABSTRACT:
PROVIDER: PRJNA1130375 | ENA |
REPOSITORIES: ENA
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Project description: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.
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