Poly(ADP-ribosyl)ation of p53 induces gene-specific transcriptional repression of MTA1

M. H. Lee, H. Na, E. J. Kim, Han Woong Lee, M. O. Lee

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The metastasis-associated protein 1 (MTA1) is overexpressed in various human cancers and is closely connected with aggressive phenotypes; however, little is known about the transcriptional regulation of the MTA1 gene. This study identified the MTA1 gene as a target of p53-mediated transrepression. The MTA1 promoter contains two putative p53 response elements (p53REs), which were repressed by the p53-inducing drug 5-fluorouracil (5-FU). Notably, 5-FU treatment decreased MTA1 expression only in p53 wild-type cells. p53 and histone deacetylases 1/2 were recruited, and acetylation of H3K9 was decreased on the promoter region including the p53REs after 5-FU treatment. Proteomics analysis of the p53 repressor complex, which was pulled down by the MTA1 promoter, revealed that the poly(ADP-ribose) polymerase 1 (PARP-1) was part of the complex. Interestingly, p53 was poly(ADP-ribose)ylated by PARP-1, and the p53-mediated transrepression of the MTA1 gene required poly(ADP-ribose)ylation of p53. In summary, we report a novel function for poly(ADP-ribose)ylation of p53 in the gene-specific regulation of the transcriptional mode of p53 on the promoter of MTA1.

Original languageEnglish
Pages (from-to)5099-5107
Number of pages9
JournalOncogene
Volume31
Issue number49
DOIs
Publication statusPublished - 2012 Dec 6

Fingerprint

p53 Genes
Adenosine Diphosphate
Neoplasm Metastasis
Poly Adenosine Diphosphate Ribose
Proteins
Fluorouracil
Response Elements
Histone Deacetylases
Acetylation
Genetic Promoter Regions
Proteomics
Phenotype
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Lee, M. H. ; Na, H. ; Kim, E. J. ; Lee, Han Woong ; Lee, M. O. / Poly(ADP-ribosyl)ation of p53 induces gene-specific transcriptional repression of MTA1. In: Oncogene. 2012 ; Vol. 31, No. 49. pp. 5099-5107.
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Poly(ADP-ribosyl)ation of p53 induces gene-specific transcriptional repression of MTA1. / Lee, M. H.; Na, H.; Kim, E. J.; Lee, Han Woong; Lee, M. O.

In: Oncogene, Vol. 31, No. 49, 06.12.2012, p. 5099-5107.

Research output: Contribution to journalArticle

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