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

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(24), P. 16714 - 16720

Published: June 7, 2024

Histone monoaminylation (

Language: Английский

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Chemical Proteomic Profiling of Protein Dopaminylation in Colorectal Cancer Cells

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(7), P. 2651 - 2660

Published: June 5, 2024

Histone dopaminylation is a newly identified epigenetic mark that plays role in the regulation of gene transcription, where an isopeptide bond formed between fifth amino acid H3 (i.e., glutamine) and dopamine. Recently, we developed chemical probe to specifically label enrich histone via bioorthogonal chemistry. Given this powerful tool, found glutamine 5 (H3Q5dop) was highly enriched colorectal tumors, which could be attributed high expression level its regulator, transglutaminase 2 (TGM2), colon cancer cells. Due enzyme promiscuity TGM2, nonhistone proteins have also been as targets; however, dopaminylated proteome cells still remains elusive. Here, utilized our from manner performed proteomics analysis. Therefore, 425 were identified, many are involved nucleic metabolism transcription pathways. More importantly, number sites successful application probe. Overall, these findings shed light on significant association cellular protein development, further suggesting targeting pathways may become promising anticancer strategy.

Language: Английский

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The Role of E3 Ubiquitin Ligase Gene FBK in Ubiquitination Modification of Protein and Its Potential Function in Plant Growth, Development, Secondary Metabolism, and Stress Response

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 821 - 821

Published: Jan. 19, 2025

As a crucial post-translational modification (PTM), protein ubiquitination mediates the breakdown of particular proteins, which plays pivotal role in large number biological processes including plant growth, development, and stress response. The ubiquitin-proteasome system (UPS) consists ubiquitin (Ub), ubiquitinase, deubiquitinating enzyme (DUB), 26S proteasome more than 80% degradation for turnover plants. For ubiquitinases, ubiquitin-activating (E1), ubiquitin-conjugating (E2), ligase (E3), FBK (F-box Kelch repeat protein) is an essential component multi-subunit E3 SCF (Skp1-Cullin 1-F-box) involved specific recognition target proteins UPS. Many genes have been identified different species, regulates growth development through affecting endogenous phytohormones as well tolerance to various biotic abiotic stresses associated with changes secondary metabolites such phenylpropanoid, phenolic acid, flavonoid, lignin, wax, etc. review summarizes significance protein, UPS degradation, possible function metabolism, response, provides systematic comprehensive understanding mechanism potential FBKs species.

Language: Английский

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Advances in the Development of Mitochondrial Pyruvate Carrier Inhibitors for Therapeutic Applications

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 223 - 223

Published: Feb. 3, 2025

The mitochondrial pyruvate carrier (MPC) is a transmembrane protein complex critical for cellular energy metabolism, enabling the transport of from cytosol into mitochondria, where it fuels citric acid cycle. By regulating this essential entry point carbon MPC pivotal maintaining balance and metabolic flexibility. Dysregulation activity has been implicated in several disorders, including type 2 diabetes, obesity, cancer, underscoring its potential as therapeutic target. This review provides an overview complex, examining structural components, regulatory mechanisms, biological functions. We explore current understanding transcriptional, translational, post-translational modifications that modulate function highlight clinical relevance dysfunction neurodegenerative diseases. Progress development MPC-targeting therapeutics discussed, with focus on challenges designing selective potent inhibitors. Emphasis placed modern approaches identifying novel inhibitors, particularly virtual screening computational strategies. establishes foundation further research medicinal chemistry promoting advances structure-based drug design to develop

Language: Английский

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SIRT5 Alleviates Apoptosis of Vascular Endothelial Cells Under Simulated Microgravity via Desuccinylation of ERO1A

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2908 - 2908

Published: March 23, 2025

The adverse effects of weightlessness on the human cardiovascular system greatly hinder process long-term and long-distance space exploration. Succinylation is an important type protein post-translational modification. However, whether succinylation modification able to play a role in altered vascular endothelial cell function under microgravity or simulated has not been reported. This study aims investigate quantitative global proteome changes lysine related proteins, seeking facilitate better understanding deconditioning microgravity. LC-MS/MS combined with bioinformatics analysis were used quantitatively detect perspectives at level. Immunoprecipitation Western blot conducted further verify alterations proteins succinylation. A total 132 differentially expressed 164 sites identified umbilical vein cells (HUVECs). Bioinformatics indicates that may potential energy metabolism. In addition, desuccinylase SIRT5 was downregulated regulated levels HUVECs Notably, overexpression effectively protected from apoptosis induced by And Lys396 ERO1A significantly increased Mechanistically, knockdown found induce through ERO1A. These results can provide new ideas for elucidating molecular mechanism dysfunction environments, key targets scientific protective measures against space.

Language: Английский

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Spatiotemporal expression of Nischarin in developing rat brain mediates neuronal migration via the PAK1/LIMK1/cofilin pathway

Neuroscience Letters, Journal Year: 2025, Volume and Issue: unknown, P. 138251 - 138251

Published: April 1, 2025

Language: Английский

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pH-Controlled chemoselective rapid azo-coupling reaction (CRACR) enables global profiling of serotonylation proteome in cancer cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 11, 2024

Serotonylation has been identified as a novel protein post-translational modification for decades, where an isopeptide bond is formed between the glutamine residue and serotonin through transamination. Transglutaminase 2 (also known TGM2 or TGase2) was proven to act main writer enzyme this PTM number of key regulatory proteins (including small GTPases, fibronectin, fibrinogen, transporter, histone H3) have characterized substrates serotonylation. However, due lack pan-specific antibodies serotonylated glutamine, precise enrichment proteomic profiling serotonylation still remain challenging. In our previous research, we developed aryldiazonium probe specifically label in bioorthogonal manner, which depended on pH-controlled chemoselective rapid azo-coupling reaction (CRACR). Here, report application photoactive aryldiazonium-biotin global proteome cancer cells. Thus, over 1,000 were from HCT 116 cells, many are highly related carcinogenesis. Moreover, sites these determined, attributed successful chemical approach. Overall, findings provided new insights into significant association cellular development, further suggesting that target TGM2-mediated monoaminylation may serve promising strategy therapeutics.

Language: Английский

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Chemical proteomic profiling of protein dopaminylation in colorectal cancer cells

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 28, 2024

ABSTRACT Histone dopaminylation is a newly identified epigenetic mark that plays role in the regulation of gene transcription, where an isopeptide bond formed between fifth amino acid residue H3 ( i.e. , glutamine) and dopamine. In our previous studies, we discovered dynamics this post-translational modification (including installation, removal, replacement) were regulated by single enzyme, transglutaminase 2 (TGM2), through reversible transamination. Recently, developed chemical probe to specifically label enrich histone via bioorthogonal chemistry. Given powerful tool, found glutamine 5 (H3Q5dop) was highly enriched colorectal tumors, which could be attributed high expression level TGM2 colon cancer cells. Due enzyme promiscuity TGM2, non-histone proteins have also been as targets on residues, however, dopaminylated proteome cells still remains elusive. Here, utilized from manner performed proteomics analysis. Therefore, 425 identified, many are involved nucleic metabolism transcription pathways. More importantly, number sites these successful application probe. Overall, findings shed light significant association cellular protein development, further suggesting block installation may become promising anti-cancer strategy. TOC

Language: Английский

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pH-Controlled Chemoselective Rapid Azo-Coupling Reaction (CRACR) Enables Global Profiling of Serotonylation Proteome in Cancer Cells

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(10), P. 4457 - 4466

Published: Aug. 29, 2024

Serotonylation has been identified as a novel protein posttranslational modification for decades, where an isopeptide bond is formed between the glutamine residue and serotonin through transamination. Transglutaminase 2 (also known TGM2 or TGase2) was proven to act main "writer" enzyme this PTM, number of key regulatory proteins (including small GTPases, fibronectin, fibrinogen, transporter, histone H3) have characterized substrates serotonylation. However, due lack pan-specific antibodies serotonylated glutamine, precise enrichment proteomic profiling serotonylation still remain challenging. In our previous research, we developed aryldiazonium probe specifically label in bioorthogonal manner, which depended on pH-controlled chemoselective rapid azo-coupling reaction. Here, report application photoactive aryldiazonium-biotin global proteome cancer cells. Thus, over 1,000 were from HCT 116 cells, many are highly related carcinogenesis. Moreover, sites these determined, attributed successful chemical approach. Overall, findings provided new insights into significant association cellular development, further suggesting that target TGM2-mediated monoaminylation may serve promising strategy therapeutics.

Language: Английский

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Cracking Lysine Crotonylation (Kcr): Enlightening a Promising Post‐Translational Modification

ChemBioChem, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 27, 2024

Abstract Lysine crotonylation (Kcr) is a recently discovered post‐translational modification (PTM). Both histone and non‐histone Kcr‐proteins have been associated with numerous diseases including cancer, acute kidney injury, HIV latency, cardiovascular disease. Histone Kcr enhances gene expression to larger extend than the extensively studied lysine acetylation (Kac), suggesting as novel potential therapeutic target. Although scientific reports on were published in last years, relevant knowledge gaps concerning this PTM its regulation still remain. To date, only few selective Kcr‐interacting proteins identified methods for enrichment of chemical proteomics analysis are lacking. The development new techniques study underexplored could then clarify function health disease hopefully accelerate therapeutics Kcr‐related Herein we briefly review what known about mechanisms current used identify their interacting partners. This report aims highlight significant target existing that research must address.

Language: Английский

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