Article Figures & Tables
Figures
- Fig. 1.
Schematic and linear representation of the domain structure and co-chaperone-binding sites of Hsp70 and Hsp90. The amino-acid residue numbers, domains and co-chaperone-binding sites are indicated. (A) Domain structure of human Hsp70. The C-terminal EEVD motif is characteristic for cytosolic Hsp70s and is involved in binding of TPR-domain-containing proteins. (B) Domain structure of human Hsp90α. The C-terminal MEEVD motif is involved in binding of TPR-domain-containing proteins. Binding sites of co-chaperones on Hsp90 are a composite of sites of interaction for mammalian and yeast Hsp90 [adapted from previous reports ( Chen and Smith, 1998; Grammatikakis et al., 1999; Young et al., 2001)].
- Table 1.
Examples of Hsp90 and Hsp70 co-chaperones, interacting molecules and cellular function
Chaperone Cellular function Co-chaperone Preferred interaction partner References Hsp90 Signal transduction Cdc37 Kinases Cutforth and Rubin, 1994; Gerber et al., 1995; Grammatikakis et al., 1999; Kimura et al., 1997; Perdew et al., 1997; Schutz et al., 1997 Hormone response PP5 (TPR) Glucocorticoid receptor Silverstein et al., 1997 Immunophilins (TPR): Hormone receptors: Cyp40 Oestrogen receptor Silverstein et al., 1997 FKBP52 Steroid receptor Davies et al., 2002; Silverstein et al., 1997 FKBP51 Progesteron/ glucocorticoid receptor Davies et al., 2002; Silverstein et al., 1997 Cell death Unknown Apaf-1 Pandey et al., 2000 Stress response Unknown HSF-1 Zou et al., 1998 Complex assembly p23 Chaperone complex Young et al., 1998 Hop Chaperone complex Prapapanich et al., 1996 Hsp70 Signal transduction Bag1 Raf-1 kinase Wang et al., 1996 Bag1 Growth factor receptors Bardelli et al., 1996 Hormone response Bag1 Hormone receptors Zeiner and Gehring, 1995 Hip Steroid receptor Prapapanich et al., 1996 Cell death Bag1 Bcl-2 Takayama et al., 1995 Unknown Apaf-1 Beere et al., 2000 Stress response Unknown HSF-1 Abravaya et al., 1992 Complex assembly Hop Chaperone complex Chen and Smith, 1998 Hdj-1 Chaperone complex Caplan et al., 1995; Dittmar et al., 1998; Kosano et al., 1998 - Fig. 2.
A model for chaperone and co-chaperone interactions with Raf-1. Chaperones and co-chaperones play a role in the maturation, activation and inactivation of Raf-1. During maturation Cdc37 (37) and Hsp90 (90) bind to the regulatory and kinase domains of Raf-1 (in white) and keep it in an inactive conformation. Dissociation of Cdc37 and Hsp90 followed by association of Ras and/or Bag1 leads to a conformational change of Raf-1 that enables its activation. Sequestration of Bag1 by Hsp70 (70) and association of 14-3-3 leads to the inactivation of Raf-1. Raf-1 co-associating and regulatory proteins other than Ras, chaperones or co-chaperones are omitted from the model for the sake of simplicity (see text for details and References).
- Fig. 3.
A model for chaperone and co-chaperone interactions with nuclear hormone receptors. Chaperones and co-chaperones play a role in the maturation and inactivation of nuclear hormone receptors. During maturation, Hsp70 (70) and Hsp(40) bind to the hormone-binding domain (HBD) of the receptor (in white), which is followed by the association of Hop and Hsp90 (90). Maturation of the aporeceptor complex is completed by dissociation of Hsp40, Hsp70 and Hop followed by association of p23 (23) and one of the immunophilins (I). Hormone binding and dissociation of Hsp90, p23 and the immunophilin changes the conformation of the receptor, which then translocates to the nucleus and activates transcription. Bag1 can associate with the activated receptor and inhibit the activities of the receptor for which it requires its Hsp70-binding domain. AD, activation domain; DB, DNA-binding domain (see text for References).
Article navigation
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- Article
- Summary
- Too much or too little is not good
- Hsp70 and Hsp90 are heat shock proteins
- Biochemical activities of Hsp70
- Biochemical activities of Hsp90
- Interaction between chaperones and signaling molecules
- Chaperones and the Ras/Raf-1 signal transduction pathway
- Chaperones and nuclear hormone aporeceptor complex assembly
- Perspectives: consequences of variations in levels of chaperones and co-chaperones
- Acknowledgements
- References
- Figures & tables
- Info & metrics
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