Implications of transcriptional coactivator CREB binding protein complexes in rheumatoid arthritis.
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 p34(SEI-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.
Nakajima
Toshihiro
T
Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, 216-8512, Japan, nakashit@marianna-u.ac.jp.
Aratani
Satoko
S
Nakazawa
Minako
M
Hirose
Takuji
T
Fujita
Hidetoshi
H
Nishioka
Kusuki
K