The c-myc oncogene is among the most commonly overexpressed genes in human cancer, c-myc encodes a basic helix-loop-helix/leucine zipper (bHLH/LZ) transcription factor (c-MYC) that activates a cascade of downstream targets that ultimately mediate cellular transformation. Although a large number of genes are regulated by c-MYC, only a few have been functionally linked to c-MYC-mediated transformation. By expression profiling, the metastasis- associated protein 1 (MTA1) gene was identified here as a target of the c-MYC oncoprotein in primary human cells, a result confirmed in human cancer cells. MTA1 itself has been previously implicated in cellular transformation, in part through its ability to regulate the epithelial-to-mesenchymal transition and metastasis. MTA1 is a component of the Mi-2/nucleosome remodeling and deacetylating (NURD) complex that contains both histone deacetylase and nucleosome remodeling activity. The data reported here demonstrate that endogenous c-MYC binds to the genomic MTA1 locus and recruits transcriptional coactivators. Most importantly, short hairpin RNA (shRNA)-mediated knockdown of MTA1 blocks the ability of c-MYC to transform mammalian cells. These data implicate MTA1 and the Mi-2/NURD complex as one of the first downstream targets of c-MYC function that are essential for the transformation potential of c-MYC.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Sep 27 2005|
- Epithelial-to-mesenchymal transition
- Nucleosome remodeling and deacetylating
ASJC Scopus subject areas