Molecular analysis of a candidate metastasis-associated gene, MTA1: Possible interaction with histone deacetylase 1

Y. Toh, S. Kuninaka, K. Endo, T. Oshiro, Y. Ikeda, H. Nakashima, H. Baba, S. Kohnoe, T. Okamura, G. L. Nicolson, K. Sugimachi

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66 Citations (Scopus)

Abstract

We previously identified a novel rat candidate metastasis-associated gene, mta1, based on its differential expression in highly metastatic cells compared to nonmetastatic cells. Furthermore, we showed that overexpression of its human counterpart, MTA1, correlated with the invasiveness or lymph node metastasis of gastric, colorectal and esophageal carcinomas. The aim of this study was to analyze the domains of the MTA1 and investigate the function(s) of this protein. Structural analysis revealed that the MTA1 protein contained a GATA-like zinc-finger domain, a leucine zipper domain, a SANT domain similar to the DNA binding domain of myb-related proteins, a src homology 3-binding domain important in protein-protein interactions, two highly acidic regions characteristic of the acidic activation domains of many transcription factors, and nuclear localization signals. Immunofluorescence staining of COS-7 cells transfected with a myc-epitope-tagged MTA 1 expression vector clearly showed nuclear localization of MTA1. Coimmunoprecipitation of myc-tagged MTA1 and FLAG-tagged histone deacetylase 1 (HDAC1), followed by western blot analysis using anti-myc and anti-FLAG monoclonal antibodies showed that MTA1 physically bound with HDAC1 in COS-7 cells. Together with the recent finding that the NURD (nucleosome remodeling and histone deacetylase activities) complex contains an MTA1-related gene product, named MTA2, MTA1 may be another component of this complex and be involved in the alteration of chromatin structure and transcription repression.

Original languageEnglish
Pages (from-to)105-111
Number of pages7
JournalJournal of Experimental and Clinical Cancer Research
Volume19
Issue number1
Publication statusPublished - 2000 Mar 1

Keywords

  • Chromatin remodeling
  • Histone deacetylase
  • Invasion and metastasis
  • MTA1
  • NURD complex
  • Transcriptional repression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Toh, Y., Kuninaka, S., Endo, K., Oshiro, T., Ikeda, Y., Nakashima, H., Baba, H., Kohnoe, S., Okamura, T., Nicolson, G. L., & Sugimachi, K. (2000). Molecular analysis of a candidate metastasis-associated gene, MTA1: Possible interaction with histone deacetylase 1. Journal of Experimental and Clinical Cancer Research, 19(1), 105-111.