XAP2 inhibits glucocorticoid receptor activity in mammalian cells.
XAP2 is member of a protein family sharing the TPR protein interaction motif. It displays close homology to the immunophilins FKBP51 and FKBP52 that act via the Hsp90 folding machinery to regulate the glucocorticoid receptor (GR). We show that XAP2 inhibits GR by reducing its responsiveness to hormone in transcriptional activation. The effect of XAP2 on GR requires its interaction with Hsp90 through the TPR motif. The PPIase-like region turned out to be enzymatically inactive. Thus, PPIase activity is not essential for the action of XAP2 on GR, similarly to FKBP51 and FKBP52.
Laenger
Anna
A
Max Planck Institute of Psychiatry, Kraepelinstrasse 10, 80804 Munich, Germany.
Lang-Rollin
Isabelle
I
Kozany
Christian
C
Zschocke
Jürgen
J
Zimmermann
Nicole
N
Rüegg
Joëlle
J
Holsboer
Florian
F
Hausch
Felix
F
Rein
Theo
T
D015153:Blotting, Western; D002460:Cell Line; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*; D020123:Sirolimus / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology
D018841:HSP90 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011965:Receptors, Glucocorticoid; C103265:aryl hydrocarbon receptor-interacting protein; D019696:Peptidylprolyl Isomerase; D020123:Sirolimus