Grap2 cyclin D interacting protein negatively regulates CREBbinding protein, inhibiting fibroblastlike synoviocyte growth.
Mol Med Rep
; 23(4)2021 04.
Article
em En
| MEDLINE
| ID: mdl-33576455
ABSTRACT
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 fibroblastlike 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 helixloophelix protein, interacted with cAMPresponse elementbinding protein (CREB)binding protein (CBP). Furthermore, GCIP repressed CREB and NFκBdependent 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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Limite:
Aged
/
Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article