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

Copyright © 2013 Elsevier Inc. All rights reserved.

Détails bibliographiques
Publié dans:Clinical immunology (Orlando, Fla.). - 1999. - 150(2014), 1 vom: 09. Jan., Seite 12-21
Auteur principal: Igarashi, Hideya (Auteur)
Autres auteurs: Hirano, Hiroyasu, Yahagi, Ayano, Saika, Taro, Ishihara, Katsuhiko
Format: Article en ligne
Langue:English
Publié: 2014
Accès à la collection:Clinical immunology (Orlando, Fla.)
Sujets:Journal Article Research Support, Non-U.S. Gov't AID Apoptosis Autoimmunity FLS H(2)O(2) Molecular immunology RA activation induced cytidine deaminase plus... fibroblast-like synoviocytes hydrogen peroxide rheumatoid arthritis. Apoptosis Regulatory Proteins Oxidants P53AIP1 protein, human RNA, Small Interfering Tumor Suppressor Protein p53 Hydrogen Peroxide BBX060AN9V
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245 1 0 |a 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 
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520 |a 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 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a AID 
650 4 |a Apoptosis 
650 4 |a Autoimmunity 
650 4 |a FLS 
650 4 |a H(2)O(2) 
650 4 |a Molecular immunology 
650 4 |a RA 
650 4 |a activation induced cytidine deaminase 
650 4 |a fibroblast-like synoviocytes 
650 4 |a hydrogen peroxide 
650 4 |a rheumatoid arthritis. 
650 7 |a Apoptosis Regulatory Proteins  |2 NLM 
650 7 |a Oxidants  |2 NLM 
650 7 |a P53AIP1 protein, human  |2 NLM 
650 7 |a RNA, Small Interfering  |2 NLM 
650 7 |a Tumor Suppressor Protein p53  |2 NLM 
650 7 |a Hydrogen Peroxide  |2 NLM 
650 7 |a BBX060AN9V  |2 NLM 
700 1 |a Hirano, Hiroyasu  |e verfasserin  |4 aut 
700 1 |a Yahagi, Ayano  |e verfasserin  |4 aut 
700 1 |a Saika, Taro  |e verfasserin  |4 aut 
700 1 |a Ishihara, Katsuhiko  |e verfasserin  |4 aut 
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773 1 8 |g volume:150  |g year:2014  |g number:1  |g day:09  |g month:01  |g pages:12-21 
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