Chemical proteomics approaches for protein post-translational modification studies

Zhang, Nan; Wu, Jinghua; Zheng, Qingfei

doi:10.1016/j.bbapap.2024.141017

Cited by 3 publications

(9 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Protein posttranslational modifications (PTMs) can significantly expand the diversity and function of cellular proteome, which play key roles in signaling transduction. 1 Due to their fundamental functions in cell signaling, 2,3 targeting the dynamics (including the installation and removal) of protein PTMs becomes a considerable therapeutic strategy for human disease treatment. 4 In general, the dynamics of protein PTMs are regulated by "writer" and "eraser" enzymes.…”

Section: ■ Introductionmentioning

confidence: 99%

“…1 However, due to the low abundance of specific protein PTM and coexistence of multiple PTMs on the digested peptide fragments, the proteomic profiling of most cellular protein PTMs still stays challenging. 1 Pan antibody-based pull-down enrichment of proteins with the specific PTM can significantly enhance the sensitivity and accuracy of proteomics analysis. 16 Bioorthogonal chemistry-based chemical proteomics is an alternative valid method for protein PTM profiling, as the development of pan antibodies against certain PTMs cannot always be successful.…”

Section: ■ Introductionmentioning

confidence: 99%

“…16 Bioorthogonal chemistry-based chemical proteomics is an alternative valid method for protein PTM profiling, as the development of pan antibodies against certain PTMs cannot always be successful. 1 Due to the lack of pan-specific antibodies and chemical tools, the proteomic profiling of protein dopaminylation in cancer cells has not been successfully performed. Recently, we have developed a bicyclononyne (BCN)-containing probe that can modify and enrich dopaminylated histone proteins in a bioorthogonal manner.…”

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Currently, mass spectrometry (MS)-based proteomics is the major approach for protein PTM analysis . However, due to the low abundance of specific protein PTM and coexistence of multiple PTMs on the digested peptide fragments, the proteomic profiling of most cellular protein PTMs still stays challenging . Pan antibody-based pull-down enrichment of proteins with the specific PTM can significantly enhance the sensitivity and accuracy of proteomics analysis .…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Chemical Proteomic Profiling of Protein Dopaminylation in Colorectal Cancer Cells

Zhang,

Gao,

Peng

et al. 2024

J. Proteome Res.

Self Cite

View full text Add to dashboard Cite

Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Chemical Proteomic Profiling of Protein Dopaminylation in Colorectal Cancer Cells

Zhang,

Gao,

Peng

et al. 2024

J. Proteome Res.

Self Cite

View full text Add to dashboard Cite

Bioorthogonal Labeling and Enrichment of Histone Monoaminylation Reveal Its Accumulation and Regulatory Function in Cancer Cell Chromatin

Zhang,

Wu,

Hossain

et al. 2024

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Histone monoaminylation (i.e., serotonylation and dopaminylation) is an emerging category of epigenetic mark occurring on the fifth glutamine (Q5) residue of H3 N-terminal tail, which plays significant roles in gene transcription. Current analysis of histone monoaminylation is mainly based on site-specific antibodies and mass spectrometry, which either lacks high resolution or is timeconsuming. In this study, we report the development of chemical probes for bioorthogonal labeling and enrichment of histone serotonylation and dopaminylation. These probes were successfully applied for the monoaminylation analysis of in vitro biochemical assays, cells, and tissue samples. The enrichment of monoaminylated histones by the probes further confirmed the crosstalk between H3Q5 monoaminylation and H3K4 methylation. Finally, combining the ex vivo and in vitro analyses based on the developed probes, we have shown that both histone serotonylation and dopaminylation are highly enriched in tumor tissues that overexpress transglutaminase 2 (TGM2) and regulate the three-dimensional architecture of cellular chromatin.

show abstract

Chemical proteomic profiling of protein dopaminylation in colorectal cancer cells

Zhang,

Gao,

Peng

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

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 residue of H3 (i.e., glutamine) and dopamine. In our previous studies, we discovered that the dynamics of this post-translational modification (including installation, removal, and replacement) were regulated by a single enzyme, transglutaminase 2 (TGM2), through reversible transamination. 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 TGM2 in colon cancer cells. Due to the enzyme promiscuity of TGM2, non-histone proteins have also been identified as targets of dopaminylation on glutamine residues, 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 modification sites of these dopaminylated proteins were identified, 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 to block the installation of protein dopaminylation may become a promising anti-cancer strategy.

show abstract

Chemical proteomics approaches for protein post-translational modification studies

Cited by 3 publications

References 62 publications

Chemical Proteomic Profiling of Protein Dopaminylation in Colorectal Cancer Cells

Chemical Proteomic Profiling of Protein Dopaminylation in Colorectal Cancer Cells

Bioorthogonal Labeling and Enrichment of Histone Monoaminylation Reveal Its Accumulation and Regulatory Function in Cancer Cell Chromatin

Chemical proteomic profiling of protein dopaminylation in colorectal cancer cells

Contact Info

Product

Resources

About