Genomes and Genes
REGULATION OF CD154 EXPRESSION
Principal Investigator: WILLIAM FREDERICK CARSON RIGBY
Abstract: CD154 overexpression is a hallmark of Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). The etiology of the overexpression of this critical immune molecule is not understood. Second, the targeting of CD154 by antibodybased approaches is limited by toxicity. These two issues underscore the need for better understanding of the regulation of CD154 biosynthesis. We have established the role of polypyrimidine tract binding (PTS) proteins in mediating CD154 mRNA turnover through binding to a 3'UTR CUrich element (CURE). These studies uncovered a novel pathway of translational regulation through a polymorphic CA repeat found in the CD154 3'UTR which regulates CD154 mRNA polyadenylation. We refer to this novel cisacting element, consisting of CA dinucleotide repeats, as the CArich element (CARE). Importantly, the CD153'UTR CA repeats are polymorphic with certain alleles associated with CD154 overexpression and the development of RA and SLE.
Funding Period: ----------------2003 - ---------------2011-
more information: NIH RePORT
- Separate cis-trans pathways post-transcriptionally regulate murine CD154 (CD40 ligand) expression: a novel function for CA repeats in the 3'-untranslated regionB JoNell Hamilton
Department of Medicine, Dartmouth Medical School, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA
J Biol Chem 283:25606-16. 2008..These findings suggest a mechanism for the association of 3'-UTR CA-rich response element polymorphisms with CD154 overexpression and the subsequent risk of autoimmune disease...
- Rituximab mediates loss of CD19 on B cells in the absence of cell deathJonathan D Jones
Division of Rheumatology, Dartmouth Hitchcock Medical Center and Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
Arthritis Rheum 64:3111-8. 2012..To evaluate loss of the B cell-specific marker CD19 after the addition of rituximab (RTX) to healthy donor blood and to determine the role of complement-mediated cytotoxicity in these cells...
- A flexible approach to studying post-transcriptional gene regulation in stably transfected mammalian cellsRalph C Nichols
Veterans Administration Research Service, Veterans Affairs Medical Center, Mailstop 151, 215 North Main Street, White River Junction, VT 05009 0001, USA
Mol Biotechnol 48:210-7. 2011....
- Increased frequency of complement C4B deficiency in rheumatoid arthritisWilliam F C Rigby
Dartmouth Medical School at Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA
Arthritis Rheum 64:1338-44. 2012..To assess the copy number variation of complement C4A and C4B genes in patients with rheumatoid arthritis (RA)...