RRC ID 61910
Author Hikasa M, Yamamoto E, Kawasaki H, Komai K, Shiozawa K, Hashiramoto A, Miura Y, Shiozawa S.
Title p21waf1/cip1 is down-regulated in conjunction with up-regulation of c-Fos in the lymphocytes of rheumatoid arthritis patients.
Journal Biochem Biophys Res Commun
Abstract Features characteristic to rheumatoid arthritis (RA) including synovial overgrowth and joint destruction are experimentally produced by augmenting c-fos gene expression. We show that cyclin dependent kinase inhibitor p21waf1/cip1, that inhibits cell proliferation, is down-regulated in conjunction with up-regulation of c-fos in the lymphocytes of patients with RA. As to the mechanism of down-regulation of p21waf1/cip1 gene expression, transfection studies in U937 cells showed that c-fos down-regulated phosphorylation and dimerization of signal transducers and activators of transcription (STAT) 1, thereby inhibiting interferon -induced transactivation of p21waf1/cip1. Phosphorylation of STAT1 was indeed decreased in the lymphocytes of patients with RA. Thus, under overexpression of c-fos gene, c-Fos inactivates STAT1 to down-regulate p21waf1/cip1 gene expression in the lymphocytes of patients with RA, and in this way may enhance proliferation of lymphocytes.
Volume 304(1)
Pages 143-7
Published 2003-4-25
DOI 10.1016/s0006-291x(03)00574-6
PII S0006291X03005746
PMID 12705898
MeSH Arthritis, Rheumatoid / genetics Arthritis, Rheumatoid / immunology Arthritis, Rheumatoid / metabolism* Cells, Cultured Cyclin-Dependent Kinase Inhibitor p21 Cyclins / genetics* Cyclins / metabolism DNA-Binding Proteins / metabolism Down-Regulation Humans Interferon-gamma / pharmacology Lymphocytes / metabolism* Models, Biological Proto-Oncogene Proteins c-fos / metabolism* Proto-Oncogene Proteins c-fos / physiology STAT1 Transcription Factor Social Control, Formal Trans-Activators / metabolism Transcriptional Activation U937 Cells Up-Regulation
IF 2.705
Human and Animal Cells U-937 DE-4(RCB0435)