Display Settings:

Format

Send to:

Choose Destination
Clin Immunol. 2014 Jan;150(1):12-21. doi: 10.1016/j.clim.2013.10.013. Epub 2013 Nov 5.

Anti-apoptotic roles for the mutant p53R248Q through suppression of p53-regulated apoptosis-inducing protein 1 in the RA-derived fibroblast-like synoviocyte cell line MH7A.

Author information

  • 1Department of Immunology and Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama 701-0192, Japan.
  • 2Department of Immunology and Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama 701-0192, Japan. Electronic address: ishihara-im@med.kawasaki-m.ac.jp.

Abstract

We previously reported that somatic mutations in the p53 gene accumulated at a higher frequency in AID(activation induced cytidine deaminase)(+) RA-FLS, which may result in the malfunction of p53, causing the tumor-like properties of RA-FLS. Among the p53 mutations identified from 3 sources of AID(+) RA-FLS, we focused on the p53R248Q mutation because it was reported to enhance the invasiveness of lung cancer cells and to have dominant-negative activity for pro-apoptotic molecules. We obtained cDNA encoding the p53R248Q mutant and introduced it into the MH7A RA-FLS cell line. P53R248Q dramatically suppressed the expression of the pro-apoptotic molecule p53AIP1 even under oxidative stress, which normally upregulates p53AIP1, leading to apoptosis. Moreover, overexpression of p53AIP1 increased apoptosis, whereas p53AIP1 knockdown rescued the cells from apoptosis. Together, these studies indicate the critical role of p53AIP1 under DNA damaging stresses for cell fate determination in RA-FLS containing the p53R248Q mutation.

Copyright © 2013 Elsevier Inc. All rights reserved.

KEYWORDS:

AID; Apoptosis; Autoimmunity; FLS; H(2)O(2); Molecular immunology; RA; activation induced cytidine deaminase; fibroblast-like synoviocytes; hydrogen peroxide; rheumatoid arthritis.

PMID:
24316591
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk