ΔNp73α regulates MDR1 expression by inhibiting p53 function
ΔNp73α regulates MDR1 expression by inhibiting p53 function
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DOI：
10.1038/sj.onc.1210862
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发表时间：
2008-04-03
期刊：
影响因子：
8
通讯作者：
Zaika, A.
中科院分区：
文献类型：
--
作者：
Vilgelm, A.;Wei, J. X.;Zaika, A.
p73蛋白是一种转录因子，是p53蛋白家族的成员，表达为多种复杂的同种型。Delta Np 73 α是p73的N-末端截短的同种型。我们发现Delta Np 73蛋白在人胃癌中上调，提示DNp 73可能在这些肿瘤中起致癌作用。尽管已经显示DNp 73 a抑制细胞凋亡并抵消化疗药物的作用，但是这种p73同种型有助于化疗药物应答的潜在机制仍有待探索。我们发现DNp 73 a上调MDR 1 mRNA和P-糖蛋白（P-gp），其参与化疗药物的转运。这种p-gp上调伴随着胃癌细胞中p-gp功能活性的增加。我们的数据表明，通过DNp 73 a上调MDR 1是介导的与p53在MDR 1启动子的相互作用。
The p73 protein is a transcription factor and member of the p53 protein family that expresses as a complex variety of isoforms. Delta Np73 alpha is an N-terminally truncated isoform of p73. We found that Delta Np73 protein is upregulated in human gastric carcinoma suggesting that DNp73 may play an oncogenic role in these tumors. Although it has been shown that DNp73a inhibits apoptosis and counteracts the effect of chemotherapeutic drugs, the underlying mechanism by which this p73 isoform contributes to chemotherapeutic drug response remains to be explored. We found that DNp73a upregulates MDR1 mRNA and p-glycoprotein (p-gp), which is involved in chemotherapeutic drug transport. This p-gp upregulation was accompanied by increased p-gp functional activity in gastric cancer cells. Our data suggest that upregulation of MDR1 by DNp73a is mediated by interaction with p53 at the MDR1 promoter.