Primary protein unfolding takes place for many diseases, including diabetes and hypoxia, and triggers a reaction in the cells called ER stress response (ERSR). ERSR is designed as a repair mechanism, but ultimately leads to cell death via apoptosis if conditions triggering protein unfolding persist (1). The molecular clue to ERSR activation is the enhancement of the expression of key molecular chaperones, including the glucose regulated protein (GRP) 78. GRP78 is the main sensor for protein folding and the main actuator of the ERSR. ..more
Target
Depositor Specified Assays
| AID | Name | Type | Comment |
|---|---|---|---|
| 504836 | Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in human glioma: Validation | confirmatory | LOPAC validation |
| 624342 | qHTS for Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in Human Glioma: Hit Validation | other | |
| 624498 | Hit Validation Western Blot Assay for Inducers of ERSR: Assessment of GRP78 Upregulation | other | |
| 624348 | qHTS for Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in Human Glioma: Hit Validation in Cytotoxic Counterscreen | other | |
| 602332 | qHTS for Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in Human Glioma: qHTS | confirmatory |
Description:
Primary protein unfolding takes place for many diseases, including diabetes and hypoxia, and triggers a reaction in the cells called ER stress response (ERSR). ERSR is designed as a repair mechanism, but ultimately leads to cell death via apoptosis if conditions triggering protein unfolding persist (1). The molecular clue to ERSR activation is the enhancement of the expression of key molecular chaperones, including the glucose regulated protein (GRP) 78. GRP78 is the main sensor for protein folding and the main actuator of the ERSR.
In a collaboration between the Southern Research Institute and the NIH Chemical Genomics Center, a cell based screen was developed that reliably uses GRP78 as a sensor to identify small molecules as inducers of ERSR. In resting conditions, GRP78 binds proteins and acts as a natural repressor. Once unfolded proteins are present in the ER, GRP78 releases some of the repressors and binds to the unfolded proteins. The release of the repressors executes the ERSR program. Using a human glioma cell line in a miniaturized, luminescent format, a high-throughput screen was developed to identify actuators of the ERSR.
(1) Soboloff, J. and S. A. Berger (2002). "Sustained ER Ca2+ depletion suppresses protein synthesis and induces activation-enhanced cell death in mast cells." J Biol Chem 277(16): 13812-20.
NIH Chemical Genomics Center [NCGC]
NIH Molecular Libraries Probe Centers Network [MLPCN]
MLPCN Grant: DA031669-01
Assay Submitter (PI): Maurizio Grimaldi, Southern Research Institute
In a collaboration between the Southern Research Institute and the NIH Chemical Genomics Center, a cell based screen was developed that reliably uses GRP78 as a sensor to identify small molecules as inducers of ERSR. In resting conditions, GRP78 binds proteins and acts as a natural repressor. Once unfolded proteins are present in the ER, GRP78 releases some of the repressors and binds to the unfolded proteins. The release of the repressors executes the ERSR program. Using a human glioma cell line in a miniaturized, luminescent format, a high-throughput screen was developed to identify actuators of the ERSR.
(1) Soboloff, J. and S. A. Berger (2002). "Sustained ER Ca2+ depletion suppresses protein synthesis and induces activation-enhanced cell death in mast cells." J Biol Chem 277(16): 13812-20.
NIH Chemical Genomics Center [NCGC]
NIH Molecular Libraries Probe Centers Network [MLPCN]
MLPCN Grant: DA031669-01
Assay Submitter (PI): Maurizio Grimaldi, Southern Research Institute
Protocol
Please see linked AIDs for a detailed protocol of each assay.
Comment
This project in on-going and will be updated with progress at a later point.
Additional Information
Grant Number: DA031669
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