人类DDA3是一种受p53和DNA损伤下调的癌蛋白。
Human DDA3 is an oncoprotein down-regulated by p53 and DNA damage.
作者信息
Hsieh Wang-Ju, Hsieh Shu-Chen, Chen Chia-Chen, Wang Fung-Fang
机构信息
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, 155 Li-Nong Street, Section 2, Taipei 112, Taiwan.
出版信息
Biochem Biophys Res Commun. 2008 May 2;369(2):567-72. doi: 10.1016/j.bbrc.2008.02.047. Epub 2008 Feb 20.
Mouse DDA3 (mDDA3) is a microtubule-associated protein that promotes cell growth. mDDA3 contains an intronic p53 binding motif that is absent in human DDA3 (hDDA3), and is transcriptionally activated during DNA damage in a p53-dependent way. We now report that hDDA3 mRNA and protein levels were suppressed by p53, as well as in DNA damaged cells harboring wild type, but not mutant-p53 expression. We have located three consensus El-Deiry decamers at -1478/-1403 of the hDDA3 gene, and shown by chromatin immunoprecipitation that p53 bound to the region. Luciferase analysis showed that the hDDA3 promoter containing the putative p53 binding motif was responsible for p53-mediated repression. Expression of hDDA3 decreased the cell's requirement for serum, furthermore, overexpression of hDDA3 mRNA was detected in hepatoma tissues. Together our results show that hDDA3 is a p53- and DNA-damage down-regulated target that exhibits oncogenic characteristics.
小鼠DDA3（mDDA3）是一种促进细胞生长的微管相关蛋白。mDDA3含有一个人类DDA3（hDDA3）中不存在的内含子p53结合基序，并且在DNA损伤期间以p53依赖的方式被转录激活。我们现在报告，hDDA3的mRNA和蛋白质水平在p53以及在具有野生型而非突变型p53表达的DNA损伤细胞中受到抑制。我们在hDDA3基因的-1478 / -1403处定位了三个共有El-Deiry十聚体，并通过染色质免疫沉淀表明p53与该区域结合。荧光素酶分析表明，含有推定p53结合基序的hDDA3启动子负责p53介导的抑制作用。hDDA3的表达降低了细胞对血清的需求，此外，在肝癌组织中检测到hDDA3 mRNA的过表达。我们的结果共同表明，hDDA3是一个p53和DNA损伤下调的靶点，具有致癌特性。
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