title: Molecular cell biology and immunobiology of mammalian rod/ring structures.
abstract: Nucleotide biosynthesis is a highly regulated process necessary for cell growth and replication. Cytoplasmic structures in mammalian cells, provisionally described as rods and rings (RR), were identified by human autoantibodies and recently shown to include two key enzymes of the CTP/GTP biosynthetic pathways, cytidine triphosphate synthetase (CTPS) and inosine monophosphate dehydrogenase (IMPDH). Several studies have described CTPS filaments in mammalian cells, Drosophila, yeast, and bacteria. Other studies have identified IMPDH filaments in mammalian cells. Similarities among these studies point to a common evolutionarily conserved cytoplasmic structure composed of a subset of nucleotide biosynthetic enzymes. These structures appear to be a conserved metabolic response to decreased intracellular GTP and/or CTP pools. Antibodies to RR were found to develop in some hepatitis C patients treated with interferon-α and ribavirin. Additionally, the presence of anti-RR antibodies was correlated with poor treatment outcome.
authors.affiliation: Department of Oral Biology, University of Florida, Gainesville, Florida, USA.
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Carcamo
authors.affiliation: Department of Oral Biology, University of Florida, Gainesville, Florida, USA.
authors.forename: S John
authors.initials: SJ
authors.lastname: Calise
authors.affiliation: Rheuma Clinic for Rheumatic Diseases, Porto Alegre, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: von Mühlen
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, Florida, USA; Department of Clinical Nursing, School of Health Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.affiliation: Department of Oral Biology, University of Florida, Gainesville, Florida, USA. Electronic address: echan@ufl.edu.
authors.forename: Edward K L
authors.initials: EK
authors.lastname: Chan
mesh_terms: D000486:Allergy and Immunology; D000818:Animals; D019731:Carbon-Nitrogen Ligases / Q000378:metabolism; D003585:Cell Biology; D022083:Cytoplasmic Structures / Q000276:immunology* / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007168:IMP Dehydrogenase / Q000378:metabolism; D008967:Molecular Biology
chemical_list: D007168:IMP Dehydrogenase; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase
keywords: Cytidine triphosphate synthetase; Embryonic stem cells; Hepatitis C; Inosine monophosphate dehydrogenase; Mycophenolic acid; Nucleotide metabolism; Ribavirin