REGULATION OF CD154 EXPRESSION

Summary

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

Top Publications

  1. pmc Separate cis-trans pathways post-transcriptionally regulate murine CD154 (CD40 ligand) expression: a novel function for CA repeats in the 3'-untranslated region
    B JoNell Hamilton
    Department of Medicine, Dartmouth Medical School, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA
    J Biol Chem 283:25606-16. 2008
  2. pmc Rituximab mediates loss of CD19 on B cells in the absence of cell death
    Jonathan D Jones
    Division of Rheumatology, Dartmouth Hitchcock Medical Center and Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
    Arthritis Rheum 64:3111-8. 2012
  3. pmc A flexible approach to studying post-transcriptional gene regulation in stably transfected mammalian cells
    Ralph 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
  4. pmc Increased frequency of complement C4B deficiency in rheumatoid arthritis
    William F C Rigby
    Dartmouth Medical School at Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA
    Arthritis Rheum 64:1338-44. 2012

Scientific Experts

Detail Information

Publications4

  1. pmc Separate cis-trans pathways post-transcriptionally regulate murine CD154 (CD40 ligand) expression: a novel function for CA repeats in the 3'-untranslated region
    B 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...
  2. pmc Rituximab mediates loss of CD19 on B cells in the absence of cell death
    Jonathan 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...
  3. pmc A flexible approach to studying post-transcriptional gene regulation in stably transfected mammalian cells
    Ralph 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
    ....
  4. pmc Increased frequency of complement C4B deficiency in rheumatoid arthritis
    William 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)...