Metastasis-associated protein 1 (MTA1) is an essential downstream effector of the c-MYC oncoprotein

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

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

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 languageEnglish (US)
Pages (from-to)13968-13973
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number39
DOIs
StatePublished - Sep 27 2005
Externally publishedYes

Keywords

  • Epithelial-to-mesenchymal transition
  • Mi-2
  • Nucleosome remodeling and deacetylating

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint Dive into the research topics of 'Metastasis-associated protein 1 (MTA1) is an essential downstream effector of the c-MYC oncoprotein'. Together they form a unique fingerprint.

  • Cite this