Nature Communications
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2024
·Vol. 15
·期 1
·1-16
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IF 14.7
Cao Shiyang,Wang Tong,Ren Yifan,Wu Gengshan,Zhang Yuan,Tan Yafang,Zhou Yazhou,Chen Hongyan,Zhang Yu,Song Yajun,Yang Ruifu,Du Zongmin
Post-translational addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins is commonly associated with a variety of stress responses and cellular processes in eukaryotes, but its potential roles in bacteria are unclear. Here, we show that protein HmwC acts as an O-GlcNAc transferase (OGT) responsible for O-GlcNAcylation of multiple proteins in Yersinia pestis , a flea-borne pathogen responsible for plague. We identify 64 O-GlcNAcylated proteins (comprising 65 sites) with differential abundance under conditions mimicking the mammalian host (Mh) and flea vector (Fv) environments. Deletion of hmwC , encoding a putative OGT, structurally distinct from any existing member of the GT41 family, results in reduced O-GlcNAcylation, reduced growth, and alterations in virulence properties and survival under stress. Purified HmwC can modify target proteins in vitro using UDP-GlcNAc as sugar donor. One of the target proteins, OsdY, promotes Y. pestis survival under oxidative stress conditions. Thus, our results support that regulation of antioxidative responses through O-GlcNAcylation may be a conserved process shared by prokaryotes and eukaryotes.
研究领域:
微生物学
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病理学
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分子生物学
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传染病学
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产品关联
DOI
PubMed
高影响因子
CELL RESEARCH
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2024
·
IF 28.1
Jian Fenglei,Wang Shen,Tian Rui,Wang Yufen,Li Chuangpeng,Li Yan,Wang Shixuan,Fang Chao,Ma Cong,Rong Yueguang
Autophagosome–lysosome fusion mediated by SNARE complexes is an essential step in autophagy. Two SNAP29-containing SNARE complexes have been extensively studied in starvation-induced bulk autophagy, while the relevant SNARE complexes in other types of autophagy occurring under non-starvation conditions have been overlooked. Here, we found that autophagosome–lysosome fusion in selective autophagy under non-starvation conditions does not require SNAP29-containing SNARE complexes, but requires the STX17-SNAP47-VAMP7/VAMP8 SNARE complex. Further, the STX17-SNAP47-VAMP7/VAMP8 SNARE complex also functions in starvation-induced autophagy. SNAP47 is recruited to autophagosomes following concurrent detection of ATG8s and PI(4,5)P 2 via its Pleckstrin homology domain. By contrast, SNAP29-containing SNAREs are excluded from selective autophagy due to inactivation by O-GlcNAcylation under non-starvation conditions. These findings depict a previously unknown, default SNARE complex responsible for autophagosome–lysosome fusion in both selective and bulk autophagy, which could guide research and therapeutic development in autophagy-related diseases.
研究领域:
细胞生物学
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分子生物学
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自噬
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DOI
PubMed
高影响因子
Journal of Functional Foods
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2024
·
IF 3.8
Xi-you Li,Xiao-yuan Gu,Bai-ling Zhou,Bun Tsoi,Wei-xi Li
Eye deformity, a noteworthy embryopathy, is intricately linked with maternal diabetes, frequently resulting in embryonic malformation or even death. In this investigation, a hyperglycemic chick embryo model was established to delve into the protective potential of tamarind shell extract (TSE) on eye development. Chick embryos were administered with TSE (at dosages of 1, 2, and 4 µg/egg) through air sac injection on embryo development day 0 (EDD0) and later exposed to D-glucose (0.4 mmol/egg) on EDD1. To validate our findings, we replicated hyperglycemic environment using D-glucose in ARPE-19 cell model. Our research unveiled that TSE proficiently counters O-GlcNAcylation of proteins in the presence of D-glucose, thereby reinstating levels of key proteins involved in eye development, including Pax6, Daam1, mTOR, and Cdc42. Furthermore, TSE was pinpointed to curtail the D-glucose concentration within the embryo eye, considerably decreasing the accumulation of reactive oxygen species and malondialdehyde accumulation in both the ARPE-19 cells and chick embryos. Beyond its fundamental role in boosting the cellular antioxidative activity, the improved expression of apoptosis-related proteins like Caspase-3, BAX, BCL-2 and other like PI3K and AKT were observed. This suggests a probable activation of the PI3K-AKT-mTOR pathway on ARPE-19 cells by TSE, thereby downregulating apoptotic proteins in ARPE-19 cells during oxidative stress. TSE may become a potent natural countermeasure against D-glucose-induced eye malformation.
研究领域:
发育生物学
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药理学
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细胞生物学
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胚胎学
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产品关联
DOI
高影响因子
ACS Central Science
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2024
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IF 12.7
Xiangfeng Meng,Yue Zhou,Lei Xu,Limu Hu,Changjiang Wang,Xiao Tian,Xiang Zhang,Yi Hao,Bo Cheng,Jing Ma,Lei Wang,Jialin Liu,Ran Xie
Glycosylation plays a pivotal role in the intricate landscape of human cholangiocarcinoma (CCA), actively participating in key pathophysiological processes driving tumor progression. Among the various glycosylation modifications, O-linked β-N-acetyl-glucosamine modification (O-GlcNAcylation) emerges as a dynamic regulator influencing diverse tumor-associated biological activities. In this study, we employed a state-of-the-art chemical proteomic approach to analyze intact glycopeptides, unveiling the critical role of O-GlcNAcylation in orchestrating Keratin 18 (K18) and its interplay with tricarboxylic acid (TCA) cycle enzymes, specifically isocitrate dehydrogenases (IDHs), to propel CCA progression. Our findings shed light on the mechanistic intricacies of O-GlcNAcylation, revealing that site-specific modification of K18 on Ser 30 serves as a stabilizing factor, amplifying the expression of cell cycle checkpoints. This molecular event intricately fosters cell cycle progression and augments cellular growth in CCA. Notably, the interaction between O-GlcNAcylated K18 and IDHs orchestrates metabolic reprogramming by down-regulating citrate and isocitrate levels while elevating α-ketoglutarate (α-KG). These metabolic shifts further contribute to the overall tumorigenic potential of CCA. Our study thus expands the current understanding of protein O-GlcNAcylation and introduces a new layer of complexity to post-translational control over metabolism and tumorigenesis.
研究领域:
癌症生物学
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分子生物学
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生物化学
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细胞生物学
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代谢学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Jiajun Yang,Siyu Hou,Yuhui Zhao,Zhaoyang Sun,Lilin Zhang,Yan Deng,Xiaoli Shang,Hanjie Yu,Zheng Li,Hongmei Li
The antidiabetic activity of the novel Buckwheat protein-derived peptide (Ala-Phe-Tyr-Arg-Trp, AFYRW) and its associated protein glycosylation have been verified. Our preliminary study demonstrates the potential of AFYRW as a therapeutic agent for diabetes, but the mechanism needs further investigation. Given the vital role of O-linked N -acetylglucosamine transferase (OGT) in diabetes mellitus and insulin resistance (IR), we focused on the underlying molecular mechanisms of them in ameliorating IR. We found AFYRW protects against hyperglycemia in diabetic mice and improves glucose metabolism in an IR cell model. Mechanistically, we demonstrated that AFYRW decreases glutamine-fructose-6-phosphate amidotransferase (GFAT) expression via X-box binding protein 1 (XBP1) in the hexosamine biosynthesis pathway (HBP), consequently decreasing OGT and stimulating the SIRT1/PGC1α pathway. Of note, the overlapping roles of increased SIRT1 and decreased OGT caused by AFYRW ameliorated IR. The data presented here show that AFYRW contributes to metabolism by directly controlling glucose homeostasis. Taken together, our study unveils that AFYRW protects against both insulin resistance and diabetes mellitus-induced hyperglycemia through OGT to regulate the SIRT1/PGC1α pathway, which provides a mechanistic basis for novel AFYRW to be a potential therapeutic agent.
研究领域:
内分泌学
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分子生物学
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糖尿病研究
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药理学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）