AIMP3 haploinsufficiency disrupts oncogene-induced p53 activation and genomic stability
AIMP3 haploinsufficiency disrupts oncogene-induced p53 activation and genomic stability
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DOI：
10.1158/0008-5472.can-05-3740
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发表时间：
2006-07-15
期刊：
影响因子：
11.2
通讯作者：
Kim, Sunghoon
中科院分区：
文献类型：
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作者：
Park, Bum-Joon;Oh, Young Sun;Kim, Sunghoon
AIMP3(以前称为p18)被证明在DNA损伤时上调P53。在这里，我们证明了AIMP3将致癌压力与P53激活相结合，以防止细胞转化。AIMP3的单等位基因缺失和AIMP3的抑制可阻断生长因子或RAS依赖的P53的诱导。AIMP3杂合子细胞对Ras或Myc等癌基因单独诱导的细胞转化敏感。转化的AIMP3(+/-)细胞出现严重的细胞分裂和染色体结构异常。因此，AIMP3通过ATM和ATR的差异激活，在p53介导的肿瘤抑制反应中发挥重要作用，并在维持基因组稳定性方面发挥重要作用。
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.