HOXA5-Twist interaction alters p53 homeostasis in breast cancer cells
HOXA5-Twist interaction alters p53 homeostasis in breast cancer cells
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DOI：
10.1074/jbc.m411018200
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发表时间：
2005-01-21
影响因子：
4.8
通讯作者：
Raman, V
中科院分区：
文献类型：
--
作者：
Stasinopoulos, IA;Mironchik, Y;Raman, V
The homeotic gene HOXA5 has been shown to play an important role in breast tumorigenesis. We have shown that loss of p53 correlated with loss of a developmentally regulated transcription factor, HOXA5, in primary breast cancer. Searching for potential protein interacting partners we found that HOXA5 binds to an antiapoptotic protein, Twist. Furthermore, Twist-overexpressing MCF-7 cells displayed a deregulated p53 response to gamma-radiation and decreased regulation of downstream target genes. Using a p53-promoter-reporter system, we demonstrated that HOXA5 could partially restore the inhibitory effects of Twist on p53 target genes. These effects are likely mediated through both the transcriptional up-regulation of p53 and the protein-protein interaction between HOXA5 and Twist. Thus, the loss of HOXA5 expression could lead to the functional activation of Twist resulting in aberrant cell cycle regulation and promoting breast carcinogenesis.
