Chemical Proteomic Profiling of Protein Dopaminylation in Colorectal Cancer Cells.

Autor:	Zhang N; Department of Radiation Oncology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.; Center for Cancer Metabolism, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States., Gao S; Human Nutrition Program, Department of Human Sciences, College of Education and Human Ecology, The Ohio State University, Columbus, Ohio 43210, United States., Peng H; Department of Radiation Oncology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.; Center for Cancer Metabolism, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States., Wu J; Department of Radiation Oncology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.; Center for Cancer Metabolism, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States., Li H; Department of Radiation Oncology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.; Center for Cancer Metabolism, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States.; Molecular, Cellular, and Developmental Biology Graduate Program, The Ohio State University, Columbus, Ohio 43210, United States., Gibson C; Department of Radiation Oncology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.; Center for Cancer Metabolism, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States., Wu S; Department of Radiation Oncology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.; Center for Cancer Metabolism, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States.; Columbus Academy, Gahanna, Ohio 43230, United States., Zhu J; Center for Cancer Metabolism, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States.; Human Nutrition Program, Department of Human Sciences, College of Education and Human Ecology, The Ohio State University, Columbus, Ohio 43210, United States., Zheng Q; Department of Radiation Oncology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.; Center for Cancer Metabolism, James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States.; Molecular, Cellular, and Developmental Biology Graduate Program, The Ohio State University, Columbus, Ohio 43210, United States.; Department of Biological Chemistry and Pharmacology, College of Medicine, The Ohio State University, Columbus, Ohio 43210, United States.
Jazyk:	angličtina
Zdroj:	Journal of proteome research [J Proteome Res] 2024 Jul 05; Vol. 23 (7), pp. 2651-2660. Date of Electronic Publication: 2024 Jun 05.
DOI:	10.1021/acs.jproteome.4c00379
Abstrakt:	Histone dopaminylation is a newly identified epigenetic mark that plays a role in the regulation of gene transcription, where an isopeptide bond is formed between the fifth amino acid of H3 (i.e., glutamine) and dopamine. Recently, we developed a chemical probe to specifically label and enrich histone dopaminylation via bioorthogonal chemistry. Given this powerful tool, we found that histone H3 glutamine 5 dopaminylation (H3Q5dop) was highly enriched in colorectal tumors, which could be attributed to the high expression level of its regulator, transglutaminase 2 (TGM2), in colon cancer cells. Due to the enzyme promiscuity of TGM2, nonhistone proteins have also been identified as dopaminylation targets; however, the dopaminylated proteome in cancer cells still remains elusive. Here, we utilized our chemical probe to enrich dopaminylated proteins from colorectal cancer cells in a bioorthogonal manner and performed the chemical proteomics analysis. Therefore, 425 dopaminylated proteins were identified, many of which are involved in nucleic acid metabolism and transcription pathways. More importantly, a number of dopaminylation sites were identified and attributed to the successful application of our chemical probe. Overall, these findings shed light on the significant association between cellular protein dopaminylation and cancer development, further suggesting that targeting these pathways may become a promising anticancer strategy.
Databáze:	MEDLINE
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