Metastasis-associated protein 1/histone deacetylase 4-nucleosome remodeling and deacetylase complex regulates phosphatase and tensin homolog gene expression and function

Sirigiri Divijendra Natha Reddy, Suresh B. Pakala, Poonam R. Molli, Neil Sahni, Narasimha Kumar Karanam, Prakriti Mudvari, Rakesh Kumar

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Metastasis-associated protein 1 (MTA1) is widely overexpressed in human cancers and is associated with malignant phenotypic changes contributing to morbidity in the associated diseases. Here we discovered for the first time that MTA1, a master chromatin modifier, transcriptionally represses the expression of phosphatase and tensin homolog (PTEN), a tumor suppressor gene, by recruiting class II histone deacetylase 4 (HDAC4) along with the transcription factor Yin-Yang 1 (YY1) onto the PTEN promoter. We also found evidence of an inverse correlation between the expression levels of MTA1 and PTEN in physiologically relevant breast cancer microarray datasets.Wefound that MTA1 up-regulation leads to a decreased expression of PTEN protein and stimulation of PI3K as well as phosphorylation of its signaling targets. Accordingly, selective down-regulation of MTA1 in breast cancer cells increases PTEN expression and inhibits stimulation of the PI3K/AKT signaling. Collectively, these findings provide a mechanistic role for MTA1 in transcriptional repression of PTEN, leading to modulation of the resulting signaling pathways.

Original languageEnglish (US)
Pages (from-to)27843-27850
Number of pages8
JournalJournal of Biological Chemistry
Volume287
Issue number33
DOIs
StatePublished - Aug 10 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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