Regulation of the amino-terminal transcription activation domain of progesterone receptor by a cofactor-induced protein folding mechanism.

Journal Article (Journal Article)

We previously identified a small basic leucine zipper (bZIP) protein, Jun dimerization protein 2 (JDP-2), that acts as a coregulator of the N-terminal transcriptional activation domain of progesterone receptor (PR). We show here that JDP-2, through interaction with the DNA binding domain (DBD), induces or stabilizes structure in the N-terminal domain in a manner that correlates with JDP-2 stimulation of transcriptional activity. Circular dichroism spectroscopy experiments showed that JDP-2 interaction caused a significant increase in overall helical content of a two-domain PR polypeptide containing the N-terminal domain and DBD and that the change in structure resides primarily in the N-terminal domain. Thermal melt curves showed that the JDP-2/PR complex is significantly more stable than either protein alone, and partial proteolysis confirmed that JDP-2 interaction alters conformation of the N-terminal domain of PR. Functional analysis of N-terminal domain mutants and receptor chimeras provides evidence that the stimulatory effect of JDP-2 on transcriptional activity of PR is mediated through an interdomain communication between the DBD and the N-terminal domain and that transcriptional activity and functional response to JDP-2 are mediated by multiple elements of the N-terminal domain as opposed to a discrete region.

Full Text

Duke Authors

Cited Authors

  • Wardell, SE; Kwok, SC; Sherman, L; Hodges, RS; Edwards, DP

Published Date

  • October 2005

Published In

Volume / Issue

  • 25 / 20

Start / End Page

  • 8792 - 8808

PubMed ID

  • 16199860

Pubmed Central ID

  • PMC1265796

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/MCB.25.20.8792-8808.2005


  • eng

Conference Location

  • United States