First Author | Stasinopoulos IA | Year | 2005 |
Journal | J Biol Chem | Volume | 280 |
Issue | 3 | Pages | 2294-9 |
PubMed ID | 15545268 | Mgi Jnum | J:96147 |
Mgi Id | MGI:3529613 | Doi | 10.1074/jbc.M411018200 |
Citation | Stasinopoulos IA, et al. (2005) HOXA5-twist interaction alters p53 homeostasis in breast cancer cells. J Biol Chem 280(3):2294-9 |
abstractText | 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 anti-apoptotic 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. |