Transcriptional activation of the nuclear receptor corepressor RIP140 by retinoic acid: A potential negative-feedback regulatory mechanism

Joanna S. Kerley, Shannon L. Olsen, Sarah J. Freemantle, Michael J. Spinella

Research output: Contribution to journalArticle

Abstract

Through the use of microarray analysis it was discovered that the nuclear receptor coregulator, receptor interacting protein 140 (RIP140), was induced early during all-trans retinoic acid (RA)-induced differentiation of human embryonal carcinoma cells. A rapid, fourfold induction of RIP140 mRNA was detected within 3 h of RA treatment in human embryonal carcinoma and MCF-7 human breast cancer cells. RIP140 protein levels were induced within 6 h of RA treatment. The RA induction of RIP140 mRNA did not require de novo protein synthesis, consistent with RIP140 being a direct transcriptional target of retinoid receptors. Promoter/enhancer elements directly upstream of the RIP140 coding region supported RA-induced transcription of a luciferase gene. In addition the ability of overexpressed RIP140 to repress ligand activated retinoid receptors was confirmed. The finding that RIP140 is a direct transcriptional target of RA is one of the first examples of acute transcriptional regulation of a nuclear receptor coactivator or corepressor. These data are consistent with a model by which RA induction of RIP140 supplies a negative feedback signal toward ligand-activated retinoid receptors.

Original languageEnglish (US)
Pages (from-to)969-975
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume285
Issue number4
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Keywords

  • MCF7, breast cancer
  • RIP140, corepressor, embryonal carcinoma
  • Retinoic acid
  • Teratocarcinoma

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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