Redox Biology, Journal Year: 2024, Volume and Issue: 78, P. 103438 - 103438
Published: Nov. 19, 2024
Language: Английский
Nature, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 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.
Language: Английский
Citations
4
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Journal Year: 2024, Volume and Issue: 1872(4), P. 141017 - 141017
Published: April 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.
Language: Английский
Citations
9
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
Citations
6
Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 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.
Language: Английский
Citations
0
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 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.
Language: Английский
Citations
0
MedComm, Journal Year: 2025, Volume and Issue: 6(4)
Published: April 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.
Language: Английский
Citations
0
Bioscience Reports, Journal Year: 2024, Volume and Issue: 44(8)
Published: Aug. 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.
Language: Английский
Citations
2
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
Citations
1
Redox Biology, Journal Year: 2024, Volume and Issue: 78, P. 103438 - 103438
Published: Nov. 19, 2024
Language: Английский
Citations
0