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MR Vol.14 No.1 indexに戻る
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MODERN RHEUMATOLOGY
Vol.14 No.1 |
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Implications of transcriptional coactivator CREB
binding protein complexes in rheumatoid arthritis |
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| Toshihiro Nakajima1 , Satoko Aratani1, Minako
Nakazawa1, Takuji Hirose1, Hidetoshi Fujita1 and Kusuki Nishioka1 |
| (1) Institute of Medical Science, St. Marianna
University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki,
216-8512, Japan |
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| Abstract |
| Abstract Transcriptional coactivators have crucial
roles in eukaryotic transcription. It has been suggested that one
of the coactivators, cAMP response element binding protein (CREB)
binding protein (CBP), regulates gene expression with a number of
transcription factors via two mechanisms. One is the recruitment
of general transcriptional machinery to the promoters. The other
is its intrinsic and associated histone acetyltransferase (HAT) activity,
which increases the accessibility of the activator to DNA, and the
acetylation of nonhistone proteins. Rheumatoid arthritis (RA) is
characterized by the inflammation and proliferation of synovium,
leading to the destruction of articular cartilage and bone. To understand
the pathogenesis of RA, we focused the transcription mechanism through
CBP in synoviocytes and chondrocytes. We identified Notch-1 in synoviocytes
and p34SEI-1 in chondrocytes as CBP binding proteins by yeast two-hybrid
screening. It was also suggested that the acetylation of p53 could
repress transactivation in RA synoviocytes. These associations may
regulate proliferation and apoptosis. This study suggests that regulation
of the coactivator could become a novel strategy for RA therapy. |
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| Key words |
| Key words CREB binding protein (CBP) - Coactivator
- Histone acetyltransferase (HAT) - Rheumatoid arthritis (RA) - Synoviocyte
- Transcription |
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