A divergent role of COOH-terminal domains in Nurrl and Nur77 transactivation

Susan O. Castillo, Qianxun Xiao, Zdenek Kostrouch, Beatrice Dozin, Vera M. Nikodem

Research output: Contribution to journalArticlepeer-review

Abstract

Orphan nuclear receptors such as Nurrl and Nur77 have conserved amino acid sequences in the zinc finger DNA binding domains and similar COOH- terminal regions, but have no known ligands. These receptors can bind DNA sequences (response elements) as monomers and can also heterodimerize with the retinoid X receptor to activate transcription. We report here the identification and initial characterization of a novel COOH-terminal truncated isoform of Nurr1, Nurr1a. Internal splicing of Nurrl generates a frameshift such that a stop codon is prematurely encoded resulting in a naturally occurring COOH-terminal truncation. Embryonic and postnatal mouse brain showed both Nurrl and Nurr1a mRNAs expressed during development. To characterize essential COOH-terminal elements that may be deleted from Nurr1a and determine function in putative ligand binding, we created COOH-terminal deletion mutants. Nurrl, Nur77, and 3'-truncated mutants bind in gel mobility shift assays to the monomeric Nur77 response element (B1A-RE). However, in transient transfection assays, a truncation of as little as 15 Nurrl COOH- terminal amino acids diminished transcriptional activation of B1A-thymidine kinase-chloramphenicol acetyltransferase reporter. This result was not seen for a similar Nur77 deletion mutant, Nur77-586. Unlike full-length Nurr1 and Nur77, transactivation by Nur77-586 was not augmented in response to the presence of retinoid-like receptor and 9-cis-retinoic acid. Thus, the interaction of putative ligand binding and transactivation for Nurrl and Nur77 may function differently.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalGene Expression
Volume7
Issue number1
Publication statusPublished - 1998

Keywords

  • 9-cis-RA
  • Nur77
  • Nurr1a Alternative splicing
  • Nurrl
  • RXR
  • Transcriptional regulation

ASJC Scopus subject areas

  • Genetics

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