RARs and RXRs: Evidence for two autonomous transactivation functions (AF-1 and AF-2) and heterodimerization in vivo

S. Nagpal, S. Friant, H. Nakshatri, P. Chambon

Research output: Contribution to journalArticle

265 Scopus citations

Abstract

We have previously reported that the AB regions of retinoic acid receptors (RARs and RXRs) contain a transcriptional activation function capable of modulating the activity of the ligand-dependent activation function present in the C-terminal DE regions of these receptors. However, we could not demonstrate that these AB regions possess an autonomous activation function similar to the AF-1s found in the AB regions of steroid hormone receptors. Using the mouse CRBPII promoter as a reporter gene, we now report that the AB regions of RARα, β and γ, as well as those of RXRα and γ contain an autonomous, ligand-independent activation function, AF-1, which can efficiently synergize with AF-2s. Moreover, AF-1s account for the ligand-independent, constitutive activation of transcription by RXRα and γ. We also show that RARs and RXRs preferentially heterodimerize in solution in cultured cells in vivo, through the dimerization interface present in their E region, irrespective of the presence of all-trans or 9-cis retinoic acid. Furthermore, our results indicate that homodimeric interactions are not observed in cultured cells in vivo under conditions where heterodimeric interactions readily occur, which is in agreement with previous observations showing the preferential binding of RAR-RXR heterodimers to RA response elements in vitro.

Original languageEnglish (US)
Pages (from-to)2349-2360
Number of pages12
JournalEMBO Journal
Volume12
Issue number6
StatePublished - Jan 1 1993
Externally publishedYes

Keywords

  • AF-1
  • AF-2
  • Autonomous transactivation functions
  • Heterodimerization
  • Retinoic acid receptors

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'RARs and RXRs: Evidence for two autonomous transactivation functions (AF-1 and AF-2) and heterodimerization in vivo'. Together they form a unique fingerprint.

  • Cite this