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) |