Journal Article

Metastasis-Associated Protein 1 (MTA1) Is an Essential Downstream Effector of the c-MYC Oncoprotein

Patel, Jagruti H., Vogt, Peter K., Yu, Duonan, DeSalle, Lauren M., Capobianco, Anthony J., Thomas-Tikhonenko, Andrei, McMahon, Steven B., Zhang, Xiao-yong

2005

Overview

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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Adenosine Triphosphatases - metabolism / Animals / Autoantigens - metabolism / Biological Sciences / Bone marrow cells / Cancer / Cell cycle / Cell growth / Cell lines / Cell Transformation, Neoplastic - genetics / Cell Transformation, Neoplastic - metabolism / DNA Helicases - metabolism / Gene expression / Gene Expression Profiling / Gene expression regulation / Gene Expression Regulation, Neoplastic / Genes / Genetics / Histone Deacetylases - genetics / Histone Deacetylases - metabolism / Histone Deacetylases - physiology / Histones / Humans / Kidney cells / Messenger RNA / Mi-2 Nucleosome Remodeling and Deacetylase Complex / Mice / Oligonucleotide Array Sequence Analysis / Proto-Oncogene Proteins c-myc - genetics / Proto-Oncogene Proteins c-myc - metabolism / Repressor Proteins - genetics / Repressor Proteins - physiology / RNA, Small Interfering - genetics / RNA, Small Interfering - pharmacology / Trans-Activators / Tumor Cells, Cultured / Tumors