98%
921
2 minutes
20
Steroidal glycoalkaloids (SGAs) are cholesterol-derived molecules produced by solanaceous species. They contribute to pathogen defence but are toxic to humans and considered as anti-nutritional compounds. Here we show that GLYCOALKALOID METABOLISM 9 (GAME9), an APETALA2/Ethylene Response Factor, related to regulators of alkaloid production in tobacco and Catharanthus roseus, controls SGA biosynthesis. GAME9 knockdown and overexpression in tomato and potato alters expression of SGAs and upstream mevalonate pathway genes including the cholesterol biosynthesis gene STEROL SIDE CHAIN REDUCTASE 2 (SSR2). Levels of SGAs, C24-alkylsterols and the upstream mevalonate and cholesterol pathways intermediates are modified in these plants. Δ(7)-STEROL-C5(6)-DESATURASE (C5-SD) in the hitherto unresolved cholesterol pathway is a direct target of GAME9. Transactivation and promoter-binding assays show that GAME9 exerts its activity either directly or cooperatively with the SlMYC2 transcription factor as in the case of the C5-SD gene promoter. Our findings provide insight into the regulation of SGA biosynthesis and means for manipulating these metabolites in crops.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756317 | PMC |
http://dx.doi.org/10.1038/ncomms10654 | DOI Listing |
Protein Pept Lett
September 2025
Department of Urology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou730000, Gansu, China.
Introduction: Dysregulation of mevalonate metabolism is a hallmark of tumorigenesis and therapy resistance across malignancies, though its role in bladder cancer remains unclear. This study aimed to elucidate its impact on prognosis and cisplatin chemosensitivity in bladder cancer.
Methods: Transcriptomic data and clinical information of bladder cancer patients were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases.
J Biol Chem
September 2025
Chemical Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Pharmacology, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA. Electronic address:
Mevalonate is a precursor for essential metabolites, such as isoprenoids and sterols. Its synthesis starts with HMGCS1 producing HMG-CoA, which is then converted to mevalonate by HMGCR, a target of statins. Cancer cells often upregulate enzymes in the mevalonate pathway (MVP) to meet their metabolic demands, leading to the development of inhibitors targeting several enzymes in this pathway.
View Article and Find Full Text PDFPLoS One
September 2025
Faculty of Health, Institute of Pharmacology and Toxicology, Centre for Biomedical Education and Research (ZBAF), School of Medicine, Witten/Herdecke University, Witten, Germany.
The emergence of antibiotic resistance continues to pose a significant global challenge. Drug repurposing, wherein existing therapeutics are evaluated for new applications, offers a promising strategy to address this issue. Farnesyltransferase inhibitors (FTIs), initially developed for cancer therapy, have demonstrated antimicrobial activity against several gram-positive bacteria.
View Article and Find Full Text PDFEur Heart J
September 2025
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
Cardiovascular disease remains a major global health challenge, with dyslipidaemia being a key modifiable risk factor. While low density lipoprotein cholesterol (LDL-C) is the primary target for lipid-lowering therapies, recent evidence highlights the importance of triglycerides, apolipoprotein B (apoB), and lipoprotein(a) [Lp(a)] for residual cardiovascular risk. Current lipid-lowering therapies target key enzymes and proteins involved in cholesterol and lipid metabolism.
View Article and Find Full Text PDFDevelopmental delay and seizures with or without movement abnormalities (OMIM 617836) caused by heterozygous pathogenic variants in the gene (DHDDS-CDG) is a rare genetic disease that belongs to the progressive encephalopathy spectrum. It results in developmental delay in affected children, accompanied by myoclonus, seizures, ataxia and tremor, which worsens over time. encodes a subunit of a DHDDS/NUS1 cis-prenyltransferase ( PTase), a branch point enzyme of the mevalonate pathway essential for N-linked glycosylation.
View Article and Find Full Text PDF