Genistein down-regulates androgen receptor by modulating HDAC6-Hsp90 chaperone function

Genistein down-regulates androgen receptor by modulating HDAC6-Hsp90 chaperone function.

Androgen receptor (AR) is a ligand-activated transcription factor belonging to the steroid hormone receptor family and is very important for the development and progression of prostate cancer. The soy isoflavone genistein has been shown previously to down-regulate AR in androgen-dependent prostate cancer cell lines such as LNCaP. However, the mechanism(s) by which AR is down-regulated by genist...

HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor.

The molecular chaperone heat shock protein 90 (Hsp90) and its accessory cochaperones function by facilitating the structural maturation and complex assembly of client proteins, including steroid hormone receptors and selected kinases. By promoting the activity and stability of these signaling proteins, Hsp90 has emerged as a critical modulator in cell signaling. Here, we present evidence that H...

The Hsp90 chaperone machinery regulates signaling by modulating ligand binding clefts.

∗ This minireview will be reprinted in the 2008 Minireview Compendium, which will be available in January, 2009. The authors’ work is currently supported by NIH Grants DA022354 and GM077430. 1 To whom correspondence should be addressed. Tel.: 734-936-5797; Fax: 734-763-4450; E-mail: [email protected] 2 The abbreviations used are: Hsp, heat shock protein; CHIP, carboxy terminus of Hsc70-interactin...

Constitutively-active androgen receptor variants function independently of the HSP90 chaperone but do not confer resistance to HSP90 inhibitors

The development of lethal, castration resistant prostate cancer is associated with adaptive changes to the androgen receptor (AR), including the emergence of mutant receptors and truncated, constitutively active AR variants. AR relies on the molecular chaperone HSP90 for its function in both normal and malignant prostate cells, but the requirement for HSP90 in environments with aberrant AR expr...

Modulating the Interdomain Interaction Regulates Androgen Receptor Function by Melanoma Antigen Gene Protein MAGE-11