Defining an N-terminal activation domain of the orphan nuclear receptor Nurr1
DOI: 10.1016/j.bbrc.2003.11.079
Title: Defining an N-terminal activation domain of the orphan nuclear receptor Nurr1
Journal Title: Biochemical and Biophysical Research Communications
Volume: 313
Issue: 1
Publication Date: 2 January 2004
Start Page: 205
End Page: 211
Published online: online 26 November 2003
ISSN: 0006-291X
Author: Mariette Nordzella, Piia Aarnisaloa1, ;rard Benoita, Diogo S Castroa2, Thomas Perlmannab
Affiliations:

  • a Ludwig Institute for Cancer Research, Stockholm Branch, Box 240, S-171 77, Stockholm, Sweden

  • b Department of Cell and Molecular Biology, Karolinska Institute, S-171 77, Stockholm, Sweden
  • Abstract: an orphan nuclear receptor essential for the development of midbrain dopaminergic neurons. Activation of Nurr1 depends on two so-called activation functions (AFs) situated in the N- and C-terminal regions, respectively. The region important for activation within the C-terminal domain has been shown to promote activation in a highly cell-type specific fashion in the absence of added exogenous ligands. In contrast, the region in the N-terminal domain (AF1) has been much less characterized. Here we mutagenized the N-terminal domain of Nurr1 to define essential activation regions. The results identified a short core activation region localized close to the N-terminus of Nurr1. In addition, cell-type specific influences by other signaling pathways were analyzed by mutagenesis of specific conserved phosphorylation sites. The results indicate that mitogen-activated protein kinase activity (MAPK) positively influences Nurr1 AF1-dependent transcriptional activation via a conserved phosphorylation site outside the core activation region.
    Received: 11 November 2003
    Email: Thomas.Perlmann@licr.ki.se

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