Engineered Methionine Adenosyltransferase Cascades for Metabolic Labeling of Individual DNA Methylomes in Live Cells DOI Creative Commons

Liepa Gasiulė,

Vaidotas Stankevičius, Kotryna Kvederavičiūtė

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(27), P. 18722 - 18729

Published: June 29, 2024

Methylation, a widely occurring natural modification serving diverse regulatory and structural functions, is carried out by myriad of S-adenosyl-l-methionine (AdoMet)-dependent methyltransferases (MTases). The AdoMet cofactor produced from l-methionine (Met) ATP family multimeric methionine adenosyltransferases (MAT). To advance mechanistic functional studies, strategies for repurposing the MAT MTase reactions to accept extended versions transferable group corresponding precursors have been exploited. Here, we used structure-guided engineering mouse MAT2A enable biocatalytic production an analogue, Ado-6-azide, synthetic S-(6-azidohex-2-ynyl)-l-homocysteine (N3-Met). Three engineered variants showed catalytic proficiency with analogues supported DNA derivatization in cascade M.TaqI variant DNMT1 both absence presence competing Met. We then installed two as MAT2A-DNMT1 cascades embryonic stem cells using CRISPR-Cas genome editing. resulting cell lines maintained normal viability methylation levels Dnmt1-dependent azide tags upon exposure N3-Met physiological This first time demonstrates genetically stable system biosynthetic which enables mild metabolic labeling DNMT-specific methylome live mammalian cells.

Language: Английский

Gut microbiota and dietary intervention: affecting immunotherapy efficacy in non–small cell lung cancer DOI Creative Commons

Yu Xin,

Chenguang Liu,

Dan Zang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 1, 2024

Non-small cell lung cancer (NSCLC) accounts for 80-85% of all cancers. In recent years, treatment with immune checkpoint inhibitors (ICIs) has gradually improved the survival rate patients NSCLC, especially those in advanced stages. ICIs can block tolerance pathways that are overexpressed by tumor cells and maintain protective activity system components against cells. Emerging clinical evidence suggests gut microbiota may modulate responses to treatment, possibly holding a key role surveillance efficacy ICIs. Studies have also shown diet influence abundance humans, therefore, dietary interventions adjustment is novel promising strategy adjunctive therapy. This review comprehensively summarizes effects microbiota, antibiotics (ATBs), intervention on immunotherapy aim informing development strategies NSCLC immunotherapy.

Language: Английский

Citations

10
Positive feedback between arginine methylation of YAP and methionine transporter SLC43A2 drives anticancer drug resistance DOI Creative Commons
Xialu Hong, Chenkai Huang, Hui Qian

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 2, 2025

Yes-associated protein (YAP) activation confers resistance to chemotherapy and targeted therapy. Methionine participates in cellular processes by converting methyl donor for the methylation of DNA, RNA protein. However, it remains unclear whether methionine affects drug influencing YAP activity. In this study, we report that deprivation remarkably suppresses transcriptional activity YAP–TEAD cancer cells. promotes PRMT1-catalyzed asymmetric dimethylation at R124 (YAP R124me2a). Mimicking abolishes reduction effect methionine-restricted diet on YAP-induced resistance. activates transcription SLC43A2, transporter, increase uptake Knockdown SLC43A2 decreases level R124me2a. BCH, inhibitor sensitizes tumors anticancer drugs. Thus, our results unravel positive feedback between contributes Disrupting could be a potential strategy While deficiency can sensitize cells therapy, Here, authors discover loop present transporter is involved multiple therapies.

Language: Английский

Citations

1
Mechanisms and rationales of SAM homeostasis DOI

Xing Zheng,

Benjamin P. Tu

Trends in Biochemical Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Methionine regulates maternal-fetal immune tolerance and endometrial receptivity by enhancing embryonic IL-5 secretion DOI Creative Commons
Shuang Cai,

Bangxin Xue,

Siyu Li

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(2), P. 115291 - 115291

Published: Feb. 1, 2025

Endometrial receptivity and maternal-fetal immune tolerance are two crucial processes for a successful pregnancy. However, the molecular mechanisms of nutrition involved largely unexplored. Here, we showed that maternal methionine supply significantly improved pregnancy outcomes, which was closely related to interleukin-5 (IL-5) concentration. Mechanistically, induced embryonic IL-5 secretion, enhanced conversion CD4+ T cells IL-5+ Th2 in uterus, thereby improving tolerance. Meanwhile, methionine-mediated secretion activated nuclear factor κB (NF-κB) pathway integrin αvβ3 expression endometrial cells, receptivity. Further, strongly influenced DNA methylation transcription levels eomesodermin (Eomes), bound directly promoter region inhibited transcription. Methionine modulated transcription, tolerance, via its effects on Eomes. This study reveals functions offers potential nutritional strategy

Language: Английский

Citations

1
PRMT5-mediated arginine methylation stabilizes GPX4 to suppress ferroptosis in cancer DOI
Yizeng Fan, Yuzhao Wang,

Weichao Dan

et al.

Nature Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Language: Английский

Citations

1
Emerging mechanisms and implications of cGAS-STING signaling in cancer immunotherapy strategies DOI Creative Commons
Jiawen Zhang, Sihui Yu, Qiao Peng

et al.

Cancer Biology and Medicine, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 20

Published: Jan. 3, 2024

The intricate interplay between the human immune system and cancer development underscores central role of immunotherapy in treatment. Within this landscape, innate system, a critical sentinel protecting against tumor incursion, is key player. cyclic GMP-AMP synthase (cGAS) stimulator interferon genes (STING) pathway has been found to be linchpin immunity: activation signaling orchestrates production type I (IFN-α/β), thus fostering maturation, differentiation, mobilization effectors microenvironment. Furthermore, STING facilitates release presentation antigens, therefore an attractive target for immunotherapy. Current strategies activate pathway, including use pharmacological agonists, have made substantial advancements, particularly when combined with checkpoint inhibitors. These approaches shown promise preclinical clinical settings, by enhancing patient survival rates. This review describes evolving understanding cGAS-STING pathway’s involvement biology therapy. Moreover, explores classical non-classical providing insights into their mechanisms action potential optimizing strategies. Despite challenges complexities, promising avenue treatment efficacy, revolutionize outcomes.

Language: Английский

Citations

8
Dietary methionine restriction in cancer development and antitumor immunity DOI
Ming Ji, Qing Xu, Xiaoling Li

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 35(5), P. 400 - 412

Published: Feb. 20, 2024

Language: Английский

Citations

8
Cancer cell-specific cGAS/STING Signaling pathway in the era of advancing cancer cell biology DOI Creative Commons
Vijay Kumar,

Caitlin Bauer,

John H. Stewart

et al.

European Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 102(3), P. 151338 - 151338

Published: July 6, 2023

Pattern-recognition receptors (PRRs) are critical to recognizing endogenous and exogenous threats mount a protective proinflammatory innate immune response. PRRs may be located on the outer cell membrane, cytosol, nucleus. The cGAS/STING signaling pathway is cytosolic PRR system. Notably, cGAS also present in cGAS-mediated recognition of dsDNA its cleavage into cGAMP activates STING. Furthermore, STING activation through downstream triggers different interferon-stimulating genes (ISGs), initiating release type 1 interferons (IFNs) NF-κB-mediated cytokines molecules. Activating generates IFN, which prevent cellular transformation cancer development, growth, metastasis. current article delineates impact cell-specific alteration tumors tumor growth This further discusses approaches specifically target cells inhibit metastasis conjunction with existing anticancer therapies.

Language: Английский

Citations

15
cGAS-STING at the crossroads in cancer therapy DOI
Rui Wang,

Aashiq Hussain,

Guo Quanquan

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2023, Volume and Issue: 193, P. 104194 - 104194

Published: Nov. 4, 2023

Language: Английский

Citations

15
Phase separation-mediated biomolecular condensates and their relationship to tumor DOI Creative Commons
Xi Wang, Jiameng Liu, Chaoming Mao

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 21, 2024

Abstract Phase separation is a cellular phenomenon where macromolecules aggregate or segregate, giving rise to biomolecular condensates resembling "droplets" and forming distinct, membrane-free compartments. This process pervasive in biological cells, contributing various essential functions. However, when phase goes awry, leading abnormal molecular aggregation, it can become driving factor the development of diseases, including tumor. Recent investigations have unveiled intricate connection between dysregulated tumor pathogenesis, highlighting its potential as novel therapeutic target. article provides an overview recent research, with particular emphasis on role tumor, implications, outlines avenues for further exploration this intriguing field.

Language: Английский

Citations

5