Celastrol inhibits Hsp90 chaperoning of steroid receptors by inducing fibrillization of the Co-chaperone p23.
J Biol Chem
; 285(6): 4224-4231, 2010 Feb 05.
Article
en En
| MEDLINE
| ID: mdl-19996313
ABSTRACT
Hsp90 is an ATP-dependent molecular chaperone. The best characterized inhibitors of Hsp90 target its ATP binding pocket, causing nonselective degradation of Hsp90 client proteins. Here, we show that the small molecule celastrol inhibits the Hsp90 chaperoning machinery by inactivating the co-chaperone p23, resulting in a more selective destabilization of steroid receptors compared with kinase clients. Our in vitro and in vivo results demonstrate that celastrol disrupts p23 function by altering its three-dimensional structure, leading to rapid formation of amyloid-like fibrils. This study reveals a unique inhibition mechanism of p23 by a small molecule that could be exploited in the dissection of protein fibrillization processes as well as in the therapeutics of steroid receptor-dependent diseases.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Triterpenos
/
Receptores de Esteroides
/
Chaperonas Moleculares
/
Proteínas HSP90 de Choque Térmico
/
Oxidorreductasas Intramoleculares
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2010
Tipo del documento:
Article