Related Experiment Video
Updated: Jul 13, 2026
11:07
Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
The glucocorticoid responses are shaped by molecular chaperones
1Département de Biologie Cellulaire, Université de Genève, Sciences III, 30 quai Ernest-Ansermet, 1211 Genève 4, Switzerland.
Molecular and Cellular Endocrinology
|July 14, 2007
Summary
Molecular chaperones, Hsp70 and Hsp90, are crucial for the glucocorticoid receptor's function. They influence its folding, activation, nuclear transport, and gene regulation, impacting physiological responses.
Area of Science:
- Molecular biology
- Cellular signaling
- Protein homeostasis
Background:
- The glucocorticoid receptor (GR) regulates numerous physiological processes.
- GR activation involves hormone binding, conformational changes, nuclear translocation, and target gene transcription.
- Molecular chaperones are essential for protein folding but their roles in protein maturation and regulation are often underestimated.
Purpose of the Study:
- To review the current understanding of how Hsp70 and Hsp90 chaperone machines influence glucocorticoid receptor (GR) activity.
- To highlight the multifaceted roles of molecular chaperones in GR's lifecycle.
Main Methods:
- Literature review of studies on Hsp70, Hsp90, and the glucocorticoid receptor.
- Analysis of research detailing chaperone involvement in protein folding, activation, transport, and degradation.
Main Results:
- Hsp70 and Hsp90 chaperones are integral to GR folding and acquisition of the active conformation.
- These chaperones facilitate GR's intracellular transport to the nucleus.
- Molecular chaperones modulate GR's transcriptional activity and influence its degradation pathways.
Conclusions:
- Hsp70 and Hsp90 play critical, underestimated roles in shaping cellular responses to glucocorticoids.
- Chaperone machinery is essential for the entire functional cycle of the glucocorticoid receptor, from synthesis to decay.
Related Concept Videos
03:00Molecular Chaperones and Protein Folding
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
03:00Molecular Chaperones and Protein Folding
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
01:26Bacterial Protein Maturation
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
01:31Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
01:22Diversity in Cell Signaling Responses
The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity.
Graded and Abrupt Responses
Some signaling systems generate...
Graded and Abrupt Responses
Some signaling systems generate...
01:37The Unfolded Protein Response
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...