Grap2 cyclin D interacting protein negatively regulates CREB‑binding protein, inhibiting fibroblast‑like synoviocyte growth

  • Authors:
    • Hidetoshi Fujita
    • Satoko Aratani
    • Toshihiro Nakajima
  • View Affiliations

  • Published online on: February 11, 2021     https://doi.org/10.3892/mmr.2021.11916
  • Article Number: 277
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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 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.
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April-2021
Volume 23 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Fujita H, Aratani S and Nakajima T: Grap2 cyclin D interacting protein negatively regulates CREB‑binding protein, inhibiting fibroblast‑like synoviocyte growth. Mol Med Rep 23: 277, 2021.
APA
Fujita, H., Aratani, S., & Nakajima, T. (2021). Grap2 cyclin D interacting protein negatively regulates CREB‑binding protein, inhibiting fibroblast‑like synoviocyte growth. Molecular Medicine Reports, 23, 277. https://doi.org/10.3892/mmr.2021.11916
MLA
Fujita, H., Aratani, S., Nakajima, T."Grap2 cyclin D interacting protein negatively regulates CREB‑binding protein, inhibiting fibroblast‑like synoviocyte growth". Molecular Medicine Reports 23.4 (2021): 277.
Chicago
Fujita, H., Aratani, S., Nakajima, T."Grap2 cyclin D interacting protein negatively regulates CREB‑binding protein, inhibiting fibroblast‑like synoviocyte growth". Molecular Medicine Reports 23, no. 4 (2021): 277. https://doi.org/10.3892/mmr.2021.11916