The Journal of Clinical Investigation’s Post

I'm glad to share our latest review article, written in collaboration with Frédéric Perros, titled "Novel Insights into the GCN2 Pathway and Its Targeting: Therapeutic Value in Cancer and Lessons from Lung Fibrosis Development," published in The FEBS Journal https://lnkd.in/d9hskDPi This review highlights recent findings on the role of GCN2 in both stressed and non-stressed cells. We also discuss its involvement in the development of cancer and lung diseases, questioning the potential of targeting GCN2 for human health benefits. We hope you find this review insightful.

New research explores the structural basis for the activation and filamentation of glutaminase, a key enzyme in cancer cell metabolism. The study uncovers the impact of phosphate and inhibitors on glutaminase activity and filament formation, shedding light on potential therapeutic targets for cancer treatment. Read more 👉 https://lnkd.in/eCinP8Wr #MolecularBiology #CancerResearch #Glutaminase #NewResearch

𝗧𝗮𝗿𝗴𝗲𝘁𝗶𝗻𝗴 𝗮𝗺𝗶𝗻𝗼 𝗮𝗰𝗶𝗱 𝗺𝗲𝘁𝗮𝗯𝗼𝗹𝗶𝘀𝗺 𝗳𝗼𝗿 𝗲𝗻𝗵𝗮𝗻𝗰𝗲𝗱 𝗶𝗺𝗺𝘂𝗻𝗼𝘁𝗵𝗲𝗿𝗮𝗽𝘆 𝗿𝗲𝘀𝗽𝗼𝗻𝘀𝗲 I have mentioned it before: I find the interaction between metabolism and immunity. This novel review does a brilliant job in discussing how amino acid metabolism drives - or rather inhibits - immune responses in cancer. It also highlights both signaling as well as other metabolic pathways that are affected by amino acids. Finally, the review discusses combinations that might improve response to immunotherapies (picture = Figure 3 of the publiation). https://lnkd.in/dmuYFhf9 Full publication: Zheng, Y., Yao, Y., Ge, T. et al. Amino acid metabolism reprogramming: shedding new light on T cell anti-tumor immunity. J Exp Clin Cancer Res42, 291 (2023). https://lnkd.in/dPA__qxp. Freely available under a Creative Commons license: https://lnkd.in/d72Y4gs6 #science #metabolism #oncology #pharmacology #precisionmedicine

This week, we sequenced RAB11B, short for Ras-related protein Rab-11B. RAB11B is a member of the RAB family of small GTPases, which are involved in the regulation of intracellular vesicle trafficking. RAB11B specifically plays a key role in the recycling of endosomes back to the plasma membrane, thereby maintaining cellular homeostasis and membrane receptor recycling. Therapeutically, targeting RAB11B has potential implications in cancer, as its dysregulation is often associated with tumorigenesis and metastasis. Additionally, RAB11B could be a candidate target for neurodegenerative therapeutics, where altered vesicle trafficking is a common feature in disorders like Alzheimer's disease. Our sequencing result demonstrates how Next-Generation Protein Sequencing™ data on the #Platinum® instrument can be used to sequence and characterize potential therapeutic targets, such as RAB11B. By analyzing the kinetic signatures from specific N-terminal amino acid recognizers, we identified 13 amino acids (F, Y, W, L, I, V, R, A, S, N, Q, E, and K), enabling identification of 4 peptides of RAB11B as shown in the figure. Discover the power of Platinum® and download our application notes here: https://lnkd.in/dsUSBvsh Which protein should be sequenced next? Let us know by commenting on this post or contact us here: https://lnkd.in/e6hVNEdm #proteomics #QSI #proteinsequencing #NGPS #biotech  

📢 Article Sharing: Role of Vav1, a hematopoietic signal transduction molecule, as an adaptor protein in health and disease #freepublication #noapc #OA 💊 Dive into the world of cell signaling and explore the fascinating control of normal cell growth and differentiation by protein-tyrosine kinases.  Intricate and precise biochemical signaling pathways result in the regulation of gene expression, cytoskeletal architecture, and cell metabolism.  🌟 Embark on this captivating exploration of the role of SH2/SH3 proteins in T cell signaling will be discussed, especially on the role of the hematopoietic signal transducer with SH2/SH3 domains, Vav1, in health and cancer. Read More and Download Full Text: https://lnkd.in/gGc4bQea #CellSignaling #SH2Domain #CellMetabolism #SignalTransduction #TCellSignalling #Health #Cancer #GeneExpression

📢 Article Sharing: Role of Vav1, a hematopoietic signal transduction molecule, as an adaptor protein in health and disease #freepublication #noapc #OA 💊 Dive into the world of cell signaling and explore the fascinating control of normal cell growth and differentiation by protein-tyrosine kinases.  Intricate and precise biochemical signaling pathways result in the regulation of gene expression, cytoskeletal architecture, and cell metabolism.  🌟 Embark on this captivating exploration of the role of SH2/SH3 proteins in T cell signaling will be discussed, especially on the role of the hematopoietic signal transducer with SH2/SH3 domains, Vav1, in health and cancer. Read More and Download Full Text: https://lnkd.in/dpR82VMZ #CellSignaling #SH2Domain #CellMetabolism #SignalTransduction #TCellSignalling #Health #Cancer #GeneExpression

Lung cancer presents significant therapeutic challenges, driving the exploration of novel treatment strategies. Programmed cell death (PCD) mechanisms are crucial in lung cancer pathogenesis and treatment response. Nutritional interventions, such as omega-3 fatty acids, modulate these pathways, offering potential therapeutic approaches. Clinical evidence supports the role of immunonutrition in enhancing PCD and improving treatment outcomes. Further research on specific molecular mechanisms is essential for translating these findings into clinical practice. Happy to share our work published online today on this new topic. #fightinglungcancer #immunonutrition #metabolism

Source: Cancers (Basel). This study used liquid chromatography and tandem mass spectrometry (LC-MS/MS) to analyze the metabolic pathways in hepatoblastoma (HB), a rare childhood tumor. The researchers compared tumor and non-tumor liver tissue samples and found 35 differentially abundant metabolites, including those involved in fatty acid transport, glycolysis, the TCA cycle, branched-chain amino acid degradation, and glutathione synthesis. Targeted metabolomics revealed reduced short-chain acylcarnitines and an accumulation of branched-chain amino acids in HB. The findings were consistent with previous transcriptomic and metabolomic data. Gene set enrichment analysis showed a downregulation of the carnitine metabolome, and immunohistochemistry confirmed a reduction in CPT1a, suggesting a lack of utilization of long-chain fatty acids in HB. The study suggests a reduced metabolic flux in HB and potential for new therapeutic targets.

#Cell: #Metabolic reprogramming is a hallmark of cancer. However, how altered metabolism in turn enhances #tumorigenicity? #Tumor cells accumulate high levels of arginine due to increased uptake and reduced arginine-to-polyamine conversion. Importantly, the high levels of #arginine promote tumor formation via further metabolic reprogramming, including changes in glucose, amino acid, #nucleotide, and fatty acid metabolism. Moreover, arginine is a second messenger-like molecule that promotes liver tumorigenesis by binding to #RBM39 and controlling metabolic gene expression. Besides, RBM39 depletion by the molecular glue degrader indisulam blocks prooncogenic metabolic reprogramming in hepatocellular carcinoma, suggesting that RBM39 is a therapeutic target in liver cancer. https://lnkd.in/gThnrptq For more push, please follow #Twitter: https://lnkd.in/gntQ9qE7 Related Product Recommendation: #dCeMM1 (https://lnkd.in/gXYx5dwy); #Indisulam (https://lnkd.in/gYBmjrru); Anti-#Cancer Metabolism Compound Library (https://lnkd.in/gJrj-quQ) Anti-Cancer #Natural Product Library (https://lnkd.in/gRqA7GKu); Small #Molecule Immuno-Oncology Compound Library (https://lnkd.in/gJVKiUaj). https://lnkd.in/gZzCGH6i

Kinases in motion…. Interesting adaptation of an enzyme complementation assay where the same protein is fused to two fragments of Renilla luciferase, one at each of the target protein's ends. As a result, luciferase complementation that leads to bioluminescence can be used to monitor conformational changes in the studied protein. This system, called Kinase Conformation (KinCon) reporter assay, has been used before but in the current study published in eLife Sciences Publications, Ltd., Eduard STEFAN and colleagues extend its application to monitoring changes in kinase conformations in response to partner protein and small molecule binding as well as to study consequences of disease-associated mutations. The kinases chosen as case studies include LKB1, BRAF, RIPK1 and CDK6, and so this method of identifying compounds that trigger opening or closing of these kinases is of interest to researchers working in the field of cancer and inflammation. Link to the paper: https://lnkd.in/e9VcqyrM #DrugDiscovery, #Cancer, #Inflammation