HSP90-dependent ATP hydrolysis promotes release of ESR:ESTG from chaperone complex

Stable Identifier
Reaction [transition]
Homo sapiens
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Release of the estrogen receptor from the chaperone complex requires requires HSP90-dependent ATP hydrolysis, and occurs at the same rate in the presence and absence of ligand (Smith et al, 1992; Smith et al, 1993; Aumais et al, 1997; Grenert et al, 1997; Obermann et al, 1998; Panaretou et al, 1998; reviewed in Smith and Toft, 2008). In the absence of ligand, released ERs are recaptured by HSP40 through its interaction with the ligand binding domain (LBD), priming reassembly of the chaperone complex. Ligand binding may result in the loss of the HSP40-binding site, allowing the receptor to escape repetitive rounds of chaperone complex assembly, and freeing it for DNA-binding (reviewed in Smith and Toft, 2008).
Literature References
PubMed ID Title Journal Year
9295332 The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation

Toft, DO, Mimnaugh, E, Fadden, P, Clark, J, Haystead, TA, Grenert, JP, Schulte, TW, Sausville, E, Krutzsch, H, Sullivan, WP, Ochel, HJ, Neckers, LM

J. Biol. Chem. 1997
9707442 ATP binding and hydrolysis are essential to the function of the Hsp90 molecular chaperone in vivo

Roe, SM, Pearl, LH, O'Brien, R, Ladbury, JE, Prodromou, C, Panaretou, B, Piper, PW

EMBO J. 1998
9817749 In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis

Russo, AA, Hartl, FU, Sondermann, H, Obermann, WM, Pavletich, NP

J. Cell Biol. 1998
1730655 Assembly of progesterone receptor with heat shock proteins and receptor activation are ATP mediated events

Stensgard, BA, Toft, DO, Welch, WJ, Smith, DF

J. Biol. Chem. 1992
7906860 Dynamics of heat shock protein 90-progesterone receptor binding and the disactivation loop model for steroid receptor complexes

Smith, DF

Mol. Endocrinol. 1993
9115298 Selective interaction of hsp90 with an estrogen receptor ligand-binding domain containing a point mutation

Lin, R, White, JH, Lee, HS, Aumais, JP

J. Biol. Chem. 1997
18451092 Minireview: the intersection of steroid receptors with molecular chaperones: observations and questions

Toft, DO, Smith, DF

Mol. Endocrinol. 2008
Catalyst Activity

ATP hydrolysis activity of ESR:ESTG:chaperone complex [nucleoplasm]

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