pH-Controlled Chemoselective Rapid Azo-Coupling Reaction (CRACR) Enables Global Profiling of Serotonylation Proteome in Cancer Cells DOI
Nan Zhang, Jinghua Wu, Shuaixin Gao

и другие.

Journal of Proteome Research, Год журнала: 2024, Номер 23(10), С. 4457 - 4466

Опубликована: Авг. 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.

Язык: Английский

Bidirectional histone monoaminylation dynamics regulate neural rhythmicity DOI Creative Commons
Qingfei Zheng, Benjamin H. Weekley,

David A. Vinson

и другие.

Nature, Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

Abstract Histone H3 monoaminylations at Gln5 represent an important family of epigenetic marks in brain that have critical roles permissive gene expression 1–3 . We previously demonstrated serotonylation 4–10 and dopaminylation 9,11–13 histone (H3Q5ser H3Q5dop, respectively) are catalysed by transglutaminase 2 (TG2), alter both local global chromatin states. Here we found TG2 additionally functions as eraser exchanger monoaminylations, including H3Q5 histaminylation (H3Q5his), which displays diurnally rhythmic contributes to circadian behaviour. H3Q5his, contrast H3Q5ser, inhibits the binding WDR5, a core member Lys4 (H3K4) methyltransferase complexes, thereby antagonizing activities on H3K4. Taken together, these data elucidate mechanism through single regulatory enzyme has ability sense chemical microenvironments affect states cells, dynamics regulation neural rhythmicity.

Язык: Английский

Процитировано

4
Chemical proteomics approaches for protein post-translational modification studies DOI Creative Commons
Nan Zhang, Jinghua Wu, Qingfei Zheng

и другие.

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Год журнала: 2024, Номер 1872(4), С. 141017 - 141017

Опубликована: Апрель 18, 2024

The diversity and dynamics of proteins play essential roles in maintaining the basic constructions functions cells. abundance functional is regulated by transcription translation processes, while alternative splicing enables same gene to generate distinct protein isoforms different lengths. Beyond transcriptional translational regulations, post-translational modifications (PTMs) are able further expand scope proteins. PTMs have been shown make significant changes surface charges, structures, activation states, interactome Due complexity, highly dynamic nature, low presence percentage, study remains challenging. Here we summarize discuss major chemical biology tools proteomics approaches enrich investigate PTM interest.

Язык: Английский

Процитировано

10
Catalytic Phosphorylation of Tyrosine via a Radical Arbuzov Reaction DOI
Benjamin D. A. Shennan,

T Fukuta,

Mina Yamane

и другие.

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

Synthetic protein/peptide modification is a powerful strategy for the development of new therapeutics and tools chemical biology. Accordingly, synthetic variant biological tyrosine phosphorylation, cornerstone post-translational landscape, could find widespread application in study this fundamental biochemical signal. This work describes mechanistically novel, redox-neutral, photocatalytic phosphorylation reaction via radical Arbuzov-type mechanism. The proceeds with good selectivity di-, tri-, oligopeptides under mild conditions near neutral pH, tolerating potentially problematic functionality. As first reaction, represents major advance toward goal phosphorylation.

Язык: Английский

Процитировано

2
Chemical Proteomic Profiling of Protein Dopaminylation in Colorectal Cancer Cells DOI
Nan Zhang, Shuaixin Gao,

Haidong Peng

и другие.

Journal of Proteome Research, Год журнала: 2024, Номер 23(7), С. 2651 - 2660

Опубликована: Июнь 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.

Язык: Английский

Процитировано

6
Transglutaminase 2-mediated Histone Monoaminylation and Its Role in Cancer DOI Creative Commons
Huapeng Li, Jinghua Wu, Nan Zhang

и другие.

Bioscience Reports, Год журнала: 2024, Номер 44(8)

Опубликована: Авг. 1, 2024

Abstract Transglutaminase 2 (TGM2) has been known as a well-characterized factor regulating the progression of multiple types cancer, due to its multifunctional activities and ubiquitous signaling pathways it is involved in. As member transglutaminase family, TGM2 catalyzes protein post-translational modifications (PTMs), including monoaminylation, amide hydrolysis, cross-linking, etc., through transamidation variant glutamine-containing substrates. Recent discoveries revealed histone an important category substrates, thus identifying monoaminylation emerging epigenetic mark, which highly enriched in cancer cells possesses significant regulatory functions gene transcription. In this review, we will summarize recent advances TGM2-mediated well role discuss key research methodologies better understand unique thereby shedding light on therapeutic potential druggable target treatment.

Язык: Английский

Процитировано

5
Phenethylaminylation: Preliminary In Vitro Evidence for the Covalent Transamidation of Psychedelic Phenethylamines to Glial Proteins using 3,5-Dimethoxy-4-(2-Propynyloxy)-Phenethylamine as a Model Compound DOI Creative Commons
Rajiv Rangan, Russell Petty, Suchismita Acharya

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 17, 2025

Abstract Psychedelics are well known for their ability to produce profoundly altered states of consciousness. But, more importantly, the effects psychedelics can influence neurobehavioral changes that last after these acute subjective end. This phenomenon is currently being leveraged in development psychedelic-assisted psychotherapies treatment multiple neuropsychiatric disorders. The cellular and molecular mechanisms by which single doses able mediate long-term cognitive an active area research. We hypothesize contribute long term state covalently modifying proteins. post-translational modification possible through transglutaminase-mediated transamidation amine termini glutamine carboxamide residues. Here, we synthesize utilize a propargylated analogue mescaline – classic serotonergic psychedelic phenethylamine found cacti species identify putative protein targets modifications use click-chemistry primary human astrocyte cell culture model. Our preliminary findings indicate diverse array glial proteins may be substrates transglutaminase 2-mediated monoaminylation our model (“phenethylaminylation”). Based on points, speculatively highlight new directions study this noncanonical activity.

Язык: Английский

Процитировано

0
Posttranslational Modification in Bone Homeostasis and Osteoporosis DOI Creative Commons

Yuzhe Lin,

Shide Jiang,

Yuming Yao

и другие.

MedComm, Год журнала: 2025, Номер 6(4)

Опубликована: Апрель 1, 2025

ABSTRACT Bone is responsible for providing mechanical protection, attachment sites muscles, hematopoiesis micssroenvironment, and maintaining balance between calcium phosphorate. As a highly active dynamically regulated organ, the formation resorption of bone crucial in development, damaged repair, mineral homeostasis, while dysregulation remodeling impairs structure strength, leading to deficiency function skeletal disorder, such as osteoporosis. Osteoporosis refers compromised mass higher susceptibility fracture, resulting from several risk factors deteriorating balanced system osteoblast‐mediated osteoclast‐mediated resorption. This strictly by translational modification, phosphorylation, methylation, acetylation, ubiquitination, sumoylation, glycosylation, ADP‐ribosylation, S‐palmitoylation, citrullination, so on. review specifically describes updating researches concerning mediated posttranslational modification. We highlight dysregulated modification osteoblast osteoclast differentiation. also emphasize involvement osteoporosis elucidate underlying molecular basis Then, we point out potential PTMs therapeutic targets. will deepen our understanding osteoporosis, identify novel targets clinical treatment future directions.

Язык: Английский

Процитировано

0
RSL3 sensitizes glioma cells to ionizing radiation by suppressing TGM2-dependent DNA damage repair and epithelial-mesenchymal transition DOI Creative Commons

Xuanzhong Wang,

Weiyan Shi,

Mengxin Li

и другие.

Redox Biology, Год журнала: 2024, Номер 78, С. 103438 - 103438

Опубликована: Ноя. 19, 2024

Язык: Английский

Процитировано

2
pH-Controlled Chemoselective Rapid Azo-Coupling Reaction (CRACR) Enables Global Profiling of Serotonylation Proteome in Cancer Cells DOI
Nan Zhang, Jinghua Wu, Shuaixin Gao

и другие.

Journal of Proteome Research, Год журнала: 2024, Номер 23(10), С. 4457 - 4466

Опубликована: Авг. 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.

Язык: Английский

Процитировано

1