RRC ID 36027
著者 Igarashi H, Hirano H, Yahagi A, Saika T, Ishihara K.
タイトル 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.
ジャーナル Clin Immunol
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.
巻・号 150(1)
ページ 12-21
公開日 2014-1-1
DOI 10.1016/j.clim.2013.10.013
PII S1521-6616(13)00291-X
PMID 24316591
MeSH Apoptosis / physiology* Apoptosis Regulatory Proteins / genetics* Arthritis, Rheumatoid Cell Line Fibroblasts Gene Knockdown Techniques Humans Hydrogen Peroxide / pharmacology Mutation Oxidants / pharmacology Oxidative Stress Phosphorylation RNA, Small Interfering / genetics Synovial Membrane / cytology Tumor Suppressor Protein p53 / genetics* Tumor Suppressor Protein p53 / metabolism
IF 3.368
引用数 3
WOS 分野 IMMUNOLOGY
リソース情報
遺伝子材料 pGL4-phTP53AIP1 (RDB07410)
ヒト・動物細胞 MH7A(RCB1512)