Functional interaction between the pro-apoptotic DAP3 and the glucocorticoid receptor.
Apoptosis is an essential process for functions such as organ development and the immune response, and glucocorticoids are one of the important regulators of the cellular functions underlying these events. We have previously shown that the pro-apoptotic death-associated protein 3 (DAP3) directly interacts with the glucocorticoid receptor (GR), leading to the enhancement of the activity of the ligand-induced receptor. Here, we show that coexpression of DAP3 and GR results in an increased amount of cellular GR, as well as in partial translocation of DAP3 to the nucleus. Although the N-terminal domain of DAP3 is sufficient for interaction with GR, the full-length DAP3 is needed to efficiently increase GR levels and enhance the transcriptional activity of GR. Since full-length DAP3 is also necessary for the pro-apoptotic effect, the interplay between the N- and C-termini of DAP3 is probably essential for its cellular function.
Hulkko
Sanna M
SM
Department of Medical Nutrition, Karolinska Institutet, Novum, S-141 86 Huddinge, Sweden.
Zilliacus
Johanna
J
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D018613:Microscopy, Confocal; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012269:Ribosomal Proteins; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; C097041:DAP3 protein, human; D005938:Glucocorticoids; D008024:Ligands; D011506:Proteins; D016601:RNA-Binding Proteins; D011965:Receptors, Glucocorticoid; D012269:Ribosomal Proteins; D003907:Dexamethasone