The pro-apoptotic protein death-associated protein 3 (DAP3) interacts with the glucocorticoid receptor and affects the receptor function

Biochem J. 2000 Aug 1;349 Pt 3(Pt 3):885-93. doi: 10.1042/bj3490885.


The yeast two-hybrid system was used to isolate cDNAs encoding proteins that interact with the glucocorticoid receptor (GR) ligand-binding domain in a ligand-dependent manner. One isolated cDNA encoded a fragment of death-associated protein 3 (DAP3), which has been implicated as a positive mediator of apoptosis. In vitro experiments showed that the full-length DAP3 also interacted with GR. The main interaction domain was mapped to the N-terminal region of DAP3 that had previously been shown to function in a dominant-negative fashion, protecting cells from apoptosis. Co-transfection experiments in COS-7 cells showed that DAP3 had a stimulatory effect on the ligand-induced transcriptional activation by GR and also increased the steroid-sensitivity. Furthermore, DAP3 formed a complex with several other nuclear receptors and some basic helix-loop-helix/Per-Arnt-Sim proteins, as well as with heat-shock protein 90 (hsp90) (Arnt is the aryl-hydrocarbon-receptor nuclear translocator, and Per and Sim are the Drosophila proteins Period and Single-minded). The results suggest that DAP3 could have an important role in GR action, possibly by modulating the cytoplasmic GR-hsp90 complex. Since glucocorticoids can induce apoptosis, the pro-apoptotic DAP3 protein may be involved in this function of GR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Binding Sites
  • COS Cells
  • Dimerization
  • Protein Binding
  • Proteins / chemistry
  • Proteins / metabolism*
  • RNA-Binding Proteins
  • Receptors, Glucocorticoid / metabolism*
  • Receptors, Glucocorticoid / physiology
  • Ribosomal Proteins
  • Transcription, Genetic
  • Two-Hybrid System Techniques


  • Apoptosis Regulatory Proteins
  • DAP3 protein, human
  • Proteins
  • RNA-Binding Proteins
  • Receptors, Glucocorticoid
  • Ribosomal Proteins