|
 |
|
|
|
EMBO reports 7, 10, 1035–1039 (2006)
doi:10.1038/sj.embor.7400778
AOP Published online: 25 August 2006
The co-chaperone XAP2 is required for activation of hypothalamic thyrotropin-releasing hormone transcription in vivo
Marie-Stéphanie Clerget Froidevaux1*, Petra Berg2*, Isabelle Seugnet1*, Stéphanie Decherf1, Nathalie Becker1, Laurent M Sachs1, Patrice Bilesimo1, Maria Nygård2, Ingemar Pongratz2 & Barbara A Demeneix1
|
|
|
|
1 UMR 5166, CNRS/MNHN USM 501, 57 rue Cuvier, Bp 32, Paris Cedex 05, France
2 Department for Biosciences and Nutrition, Karolinska Institute, 141-57 Huddinge, Sweden
To whom correspondence should be addressed
Barbara A Demeneix Tel/Fax: +33 1 40 79 36 07; E-mail: demeneix@mnhn.fr
* These authors contributed equally to this work
Received 30 January 2006; Accepted 12 July 2006; Published online 25 August 2006.
|
|
|
|
Abstract
Transcriptional control of hypothalamic thyrotropin-releasing hormone (TRH) integrates central regulation of the hypothalamo-hypophyseal-thyroid axis and hence thyroid hormone (triiodothyronine (T3)) homeostasis. The two  thyroid hormone receptors, TR1 and TR2, contribute to T3 feedback on TRH, with TR1 having a more important role in the activation of TRH transcription. How TR1 fulfils its role in activating TRH gene transcription is unknown. By using a yeast two-hybrid screening of a mouse hypothalamic complementary DNA library, we identified a novel partner for TR1, hepatitis virus B X-associated protein 2 (XAP2), a protein first identified as a co-chaperone protein. TR–XAP2 interactions were TR isoform specific, being observed only with TR1, and were enhanced by T3 both in yeast and mammalian cells. Furthermore, small inhibitory RNA-mediated knockdown of XAP2 in vitro affected the stability of TR1. In vivo, siXAP2 abrogated specifically TR1-mediated (but not TR2) activation of hypothalamic TRH transcription. This study provides the first in vivo demonstration of a regulatory, physiological role for XAP2.
|
|
top  |
|
|
|
