Celastrol inhibits Hsp90 chaperoning of steroid receptors by inducing fibrillization of the co-chaperone p23

Ahmed Chadli, Sara J. Felts, Qin Wang, William P. Sullivan, Maria Victoria Botuyan, Abdul Fauq, Marina Ramirez-Alvarado, Georges Mer

Research output: Contribution to journalArticle

58 Scopus citations


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-chaper-one 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.

Original languageEnglish (US)
Pages (from-to)4224-4231
Number of pages8
JournalJournal of Biological Chemistry
Issue number6
StatePublished - Feb 5 2010


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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