Farnesyl pyrophosphate (FPP) is utilized for many cellular processes, including the production of dolichols, ubiquinone (CoQ), sterols, farnesylated heme A and prenylated proteins. This lipid synthesized by FPP synthetase (ERG20) becomes attached to target proteins by the prenyltransferases, CDC43/RAM2 and RAM1/RAM2 complexes after the formation of the C15 and C20 units, respectively. Defects in protein prenylation as a result of inhibiting these enzyme complexes lead to pleiotropic effects in all eukaryotes. In this study, using Candida glabrata conditional mutants, the importance of the ERG20 and RAM2 genes for growth using both in vivo and in vitro assays was assessed by placing the RAM2 and ERG20 genes under the control of a regulatable promoter. Repression of RAM2 gene expression revealed growth defects under both conditions. However, repression of ERG20 gene expression did not impair fungal growth in a mouse host, but did result in growth defects on laboratory media. Thus, FPP synthase is not required for survival in an infected mouse, but the RAM2-encoded prenyltransferase was critical for growth under both conditions. This study strongly suggests that inhibitors of prenyltransferase may be promising antifungals.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1574-6968.2010.02205.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Toxicity of antimony in housefly after whole-life-cycle exposure: Changes in growth, development, redox homeostasis, mitochondrial function, and fecundity.
Ecotoxicol Environ Saf
January 2025
Key Laboratory of Zoological Systematics and Application, College of Life Sciences, Hebei University, Baoding 071002, China. Electronic address:
The increasing utilization of antimony (Sb) in manufacturing industries has led to the emergence of Sb contamination in the environment as a significant public health concern. To elucidate the toxicity of Sb and its mechanism of action, this study aimed to investigate the adverse effects of Sb on a cosmopolitan insect, housefly (Musca domestica), under a whole life cycle (from embryonic to adult stage) exposure through the examination of a suite of parameters, including biological, physiological, behavioral, and molecular endpoints. A range of Sb concentrations, including moderate contamination (0.
View Article and Find Full Text PDFEffects of RARα ligand binding domain mutations on breast fibroepithelial tumor function and signaling.
NPJ Breast Cancer
January 2025
Cancer Science Institute of Singapore, National University of, Singapore, Singapore.
Point mutations in the ligand binding domain of retinoic acid receptor alpha (RARα) are linked to breast fibroepithelial tumor development, but their role in solid tumorigenesis is unclear. In this study, we assessed the functional effects of known RARα mutations on retinoic acid signaling using biochemical and cellular assays. All tested mutants exhibited reduced transcriptional activity compared to wild-type RARα and showed a dominant negative effect, a feature associated with developmental defects and tumor formation.
View Article and Find Full Text PDFDecellularized cartilage tissue bioink formulation for osteochondral graft development.
Biomed Mater
January 2025
Department of Orthopaedic Surgery, University of Connecticut, Chemical, Materials & Biomolecular Engineering MC-3711, ARB7-E7018, 263 Farmington Avenue, Farmington, CT 06032, USA, Storrs, Connecticut, 06269, UNITED STATES.
Articular cartilage and osteochondral defect repair and regeneration presents significant challenges to the field of tissue engineering (TE). TE and regenerative medicine strategies utilizing natural and synthetic-based engineered scaffolds have shown potential for repair, however, they face limitations in replicating the intricate native microenvironment and structure to achieve optimal regenerative capacity and functional recovery. Herein, we report the development of a cartilage extracellular matrix (ECM) as a printable biomaterial for tissue regeneration.
View Article and Find Full Text PDFDefective removal of invariant chain peptides from MHC class II suppresses tumor antigen presentation and promotes tumor growth.
Cell Rep
January 2025
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
Tumor-draining lymph node dendritic cells (DCs) are poor stimulators of tumor antigen-specific CD4 T cells; however, the mechanism behind this defect is unclear. We now show that, in tumor-draining lymph node DCs, a large proportion of major histocompatibility complex class II (MHC-II) molecules retains the class II-associated invariant chain peptide (CLIP) fragment of the invariant chain bound to the MHC-II peptide binding groove due to reduced expression of the peptide editor H2-M and enhanced activity of the CLIP-generating proteinase cathepsin S. The net effect of this is that MHC-II molecules are unable to efficiently bind antigenic peptides.
View Article and Find Full Text PDFRadiation therapy for childhood-onset craniopharyngioma: systematic review and meta-analysis.
J Neurooncol
January 2025
Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, 100045, China.
Background: Craniopharyngioma (CP), a benign tumor originating from remnants of Rathke's pouch in the sellar region, accounts for approximately 30% of all cases of craniopharyngioma. Radiation therapy has been used to treat CP patients for decades; however, there is still a lack of systematic reviews on the long-term tumor control outcomes in pediatric CP patients treated with external radiation therapy.
Methods: We conducted a comprehensive search of multiple databases for studies on the tumor progression rates of childhood-onset CP(COCP) patients who received external radiotherapy.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!