Open AccessGrap2 cyclin D interacting protein negatively regulates CREB‑binding protein, inhibiting fibroblast‑like synoviocyte growth
Author(s) -
Hidetoshi Fujita,
Satoko Aratani,
Takeshi Nakajima
Publication year - 2021
Publication title -
molecular medicine reports
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2021.11916
Subject(s) - creb , cyclin d1 , coactivator , microbiology and biotechnology , creb binding protein , biology , cancer research , downregulation and upregulation , retinoblastoma protein , cyclin d , cyclin a , small interfering rna , cyclin , cell cycle , transfection , transcription factor , apoptosis , gene , biochemistry
Rheumatoid arthritis (RA) is one of the most critical articular diseases, which is characterized by synovial hyperplasia and impaired quality of life. The clinical features of RA include chronic inflammation of the joints associated with synovial cell overgrowth. However, the mechanism regulating the outgrowth of fibroblast‑like synoviocytes (FLS) is not fully understood. The present study reported that grap2 cyclin D interacting protein (GCIP), an inhibitor of DNA binding/differentiation (ID)‑like helix‑loop‑helix protein, interacted with cAMP‑response element‑binding protein (CREB)‑binding protein (CBP). Furthermore, GCIP repressed CREB‑ and NF‑κB‑dependent gene expression by inhibiting CBP binding to RNA polymerase II complexes. GCIP depletion via small interfering RNA enhanced FLS growth, whereas stable GCIP expression suppressed the growth of 293 cells. In addition, GCIP depletion in FLS induced the expression of cyclin D1, a CREB target gene. The present study identified a novel inhibitory mechanism in which an ID protein may functionally target the transcriptional coactivator CBP. These results suggested that GCIP downregulation may be pivotal in FLS outgrowth.