Related Experiment Video
Updated: May 3, 2026
11:07
Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
14.4K
Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function
Regina T Knapp1, Michael J H Wong2, Lorenz K Kollmannsberger1
1Max Planck Institute of Psychiatry, Chaperone Research Group, Munich, Germany.
Plos One
|January 24, 2014
Summary
Heat shock protein binding protein 1 (HspBP1) and Bcl2-associated athanogene 1 (BAG-1) differentially regulate steroid receptor activity by impacting Hsp70 chaperone complexes. HspBP1 inhibits glucocorticoid receptor, mineralocorticoid receptor, and androgen receptor function.
Area of Science:
- Molecular Biology
- Cellular Biology
- Protein Folding
Background:
- Heat shock protein 70 (Hsp70) chaperones are crucial for protein folding, with nucleotide exchange factors like HspBP1 and BAG-1 regulating their activity.
- Steroid receptors (e.g., GR, MR, AR) are key Hsp70 client proteins, and their proper folding and activity are essential for cellular function.
- The distinct roles of HspBP1 and BAG-1 in modulating steroid receptor physiology remain incompletely understood.
Purpose of the Study:
- To compare the influence of HspBP1 and BAG-1M on Hsp70-mediated steroid receptor folding complexes.
- To investigate the differential effects of HspBP1 and BAG-1M on the activity of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and androgen receptor (AR).
Main Methods:
- Coimmunoprecipitation assays to analyze protein-protein interactions within folding complexes.
- Pull-down assays to assess Hsp70 binding to the ligand-binding domain of GR.
- Reporter gene assays to quantify the activity of GR, MR, and AR under varying conditions.
Main Results:
- Coimmunoprecipitation revealed preferential binding of Hsp40 and steroid receptors to BAG-1M compared to HspBP1.
- HspBP1, but not BAG-1M, reduced Hsp70 binding to the GR ligand-binding domain.
- HspBP1 inhibited GR, MR, and AR activity across a broad range of protein levels and hormone concentrations.
- BAG-1M showed a dose-dependent effect, transitioning from stimulation at low levels to inhibition at higher levels.
Conclusions:
- HspBP1 and BAG-1M exert differential impacts on the composition of steroid receptor folding complexes.
- These proteins differentially modulate steroid receptor function, with significant implications for steroid receptor physiology.
- HspBP1 demonstrates a predominantly inhibitory role on GR, MR, and AR activity.
Related Concept Videos
01:45Regulation of Nuclear Protein Sorting
2.5K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.5K
01:31Transducer Mechanism: Nuclear Receptors
6.6K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
6.6K
02:04Covalently Linked Protein Regulators
8.2K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
8.2K
02:04Covalently Linked Protein Regulators
1.3K
1.3K
01:15Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
02:04Co-activators and Co-repressors
7.0K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.0K