Retinoic acid receptors initiate induction of the cytomegalovirus enhancer in embryonal cells

Peter Ghazal, Cordell Demattei, Emi Giulietti, Steven A. Kliewer, Kazuhiko Umesono, Ronald M. Evans

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Reactivation of latent virus is believed to result from a signal transduction event that induces immediateearly (IE) gene transcription. Evidence is presented that the major IE promoter (MIEP) of human cytomegalovirus (hCMV) is activated by physiological levels of retinoic acid (RA) in human embryonal carcinoma cells. Mutagenesis experiments localized in the MIEP enhancer, a retinoic acidresponsive element composed of a direct repeat separated by five nucleotides. Protein-DNA binding experiments revealed that this element functions as a specific target site for the direct interaction of nuclear receptor proteins for RA. These findings implicate the biologically active derivative of vitamin A (RA) as a potential modulator of hCMV pathogenesis in infants and immunocompromised adults.

Original languageEnglish (US)
Pages (from-to)7630-7634
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume89
Issue number16
DOIs
StatePublished - 1992

Keywords

  • Congenital defects
  • Hormone response element
  • Human cytomegalovirus
  • Pathogenesis
  • Vitamin A

ASJC Scopus subject areas

  • General

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