RRC ID |
61910
|
著者 |
Hikasa M, Yamamoto E, Kawasaki H, Komai K, Shiozawa K, Hashiramoto A, Miura Y, Shiozawa S.
|
タイトル |
p21waf1/cip1 is down-regulated in conjunction with up-regulation of c-Fos in the lymphocytes of rheumatoid arthritis patients.
|
ジャーナル |
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.
|
巻・号 |
304(1)
|
ページ |
143-7
|
公開日 |
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 |
2.985
|
リソース情報 |
ヒト・動物細胞 |
U-937 DE-4(RCB0435) |