Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function.
Hsp70 binding protein 1 (HspBP1) and Bcl2-associated athanogene 1 (BAG-1), the functional orthologous nucleotide exchange factors of the heat shock protein 70 kilodalton (Hsc70/Hsp70) chaperones, catalyze the release of ADP from Hsp70 while inducing different conformational changes of the ATPase dom...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3891853?pdf=render |
| _version_ | 1819264829787996160 |
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| author | Regina T Knapp Michael J H Wong Lorenz K Kollmannsberger Nils C Gassen Anja Kretzschmar Jürgen Zschocke Kathrin Hafner Jason C Young Theo Rein |
| author_facet | Regina T Knapp Michael J H Wong Lorenz K Kollmannsberger Nils C Gassen Anja Kretzschmar Jürgen Zschocke Kathrin Hafner Jason C Young Theo Rein |
| author_sort | Regina T Knapp |
| collection | DOAJ |
| description | Hsp70 binding protein 1 (HspBP1) and Bcl2-associated athanogene 1 (BAG-1), the functional orthologous nucleotide exchange factors of the heat shock protein 70 kilodalton (Hsc70/Hsp70) chaperones, catalyze the release of ADP from Hsp70 while inducing different conformational changes of the ATPase domain of Hsp70. An appropriate exchange rate of ADP/ATP is crucial for chaperone-dependent protein folding processes. Among Hsp70 client proteins are steroid receptors such as the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), and the androgen receptor (AR). BAG-1 diversely affects steroid receptor activity, while to date the influence of HspBP1 on steroid receptor function is mostly unknown. Here, we compared the influence of HspBP1 and BAG-1M on Hsp70-mediated steroid receptor folding complexes and steroid receptor activity. Coimmunoprecipitation studies indicated preferential binding of Hsp40 and the steroid receptors to BAG-1M as compared to HspBP1. Furthermore, Hsp70 binding to the ligand-binding domain of GR was reduced in the presence of HspBP1 but not in the presence of BAG-1M as shown by pull-down assays. Reporter gene experiments revealed an inhibitory effect on GR, MR, and AR at a wide range of HspBP1 protein levels and at hormone concentrations at or approaching saturation. BAG-1M exhibited a transition from stimulatory effects at low BAG-1M levels to inhibitory effects at higher BAG-1M levels. Overall, BAG-1M and HspBP1 had differential impacts on the dynamic composition of steroid receptor folding complexes and on receptor function with important implications for steroid receptor physiology. |
| first_indexed | 2024-12-23T20:35:42Z |
| format | Article |
| id | doaj.art-f646c17951414cd8b067fdfcea33ed82 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T20:35:42Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f646c17951414cd8b067fdfcea33ed822022-12-21T17:32:06ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8541510.1371/journal.pone.0085415Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function.Regina T KnappMichael J H WongLorenz K KollmannsbergerNils C GassenAnja KretzschmarJürgen ZschockeKathrin HafnerJason C YoungTheo ReinHsp70 binding protein 1 (HspBP1) and Bcl2-associated athanogene 1 (BAG-1), the functional orthologous nucleotide exchange factors of the heat shock protein 70 kilodalton (Hsc70/Hsp70) chaperones, catalyze the release of ADP from Hsp70 while inducing different conformational changes of the ATPase domain of Hsp70. An appropriate exchange rate of ADP/ATP is crucial for chaperone-dependent protein folding processes. Among Hsp70 client proteins are steroid receptors such as the glucocorticoid receptor (GR), the mineralocorticoid receptor (MR), and the androgen receptor (AR). BAG-1 diversely affects steroid receptor activity, while to date the influence of HspBP1 on steroid receptor function is mostly unknown. Here, we compared the influence of HspBP1 and BAG-1M on Hsp70-mediated steroid receptor folding complexes and steroid receptor activity. Coimmunoprecipitation studies indicated preferential binding of Hsp40 and the steroid receptors to BAG-1M as compared to HspBP1. Furthermore, Hsp70 binding to the ligand-binding domain of GR was reduced in the presence of HspBP1 but not in the presence of BAG-1M as shown by pull-down assays. Reporter gene experiments revealed an inhibitory effect on GR, MR, and AR at a wide range of HspBP1 protein levels and at hormone concentrations at or approaching saturation. BAG-1M exhibited a transition from stimulatory effects at low BAG-1M levels to inhibitory effects at higher BAG-1M levels. Overall, BAG-1M and HspBP1 had differential impacts on the dynamic composition of steroid receptor folding complexes and on receptor function with important implications for steroid receptor physiology.http://europepmc.org/articles/PMC3891853?pdf=render |
| spellingShingle | Regina T Knapp Michael J H Wong Lorenz K Kollmannsberger Nils C Gassen Anja Kretzschmar Jürgen Zschocke Kathrin Hafner Jason C Young Theo Rein Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function. PLoS ONE |
| title | Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function. |
| title_full | Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function. |
| title_fullStr | Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function. |
| title_full_unstemmed | Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function. |
| title_short | Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function. |
| title_sort | hsp70 cochaperones hspbp1 and bag 1m differentially regulate steroid hormone receptor function |
| url | http://europepmc.org/articles/PMC3891853?pdf=render |
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