AIMP3 haploinsufficiency disrupts oncogene-induced p53 activation and genomic stability

被引：53
作者：
Park, Bum-Joon
Oh, Young Sun
Park, Seung Yong
Choi, So Jung
Rudolph, Cornelia
Schlegelberger, Brigitte
Kim, Sunghoon [1 ]
机构：
[1] Seoul Natl Univ, Coll Pharm, Natl Creat Res Initiat, Ctr ARS Network, Seoul 151742, South Korea
[2] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany
来源：
CANCER RESEARCH | 2006年 / 66卷 / 14期
关键词：
D O I：
10.1158/0008-5472.CAN-05-3740
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
AIMP3 (previously known as p18) was shown to up-regulate p53 in response to DNA damage. Here, we show that AIMP3 couples oncogenic stresses to p53 activation to prevent cell transformation. Growth factor- or Ras-dependent induction of p53 was blocked by single allelic loss of AIMP3 as well as by suppression of AIMP3. AIMP3 heterozygous cells became susceptible to cell transformation induced by oncogenes such as Ras or Myc alone. The transformed AIMP3(+/-) cells showed severe abnormality in cell division and chromosomal structure. Thus, AIMP3 plays crucial roles in p53-mediated tumor-suppressive response against oncogenic stresses via differential activation of ATM and ATR, and in the maintenance of genomic stability.
引用
收藏
页码：6913 / 6918
页数：6
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