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Updated: Jul 22, 2025
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Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
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REDD1 (regulated in development and DNA damage 1) modulates the glucocorticoid receptor function in keratinocytes
D A Chudakova1,2, D Trubetskoy1, G Baida1
1Department of Dermatology, Northwestern University, Chicago, Illinois, USA.
Experimental Dermatology
|July 24, 2023
Summary
REDD1, a target gene of glucocorticoids (GCs), plays a crucial role in GC receptor (GR) signaling. Its absence significantly reduces GC response, suggesting a feed-forward loop for safer therapies.
Area of Science:
- Dermatology
- Molecular Biology
- Cell Biology
Background:
- Glucocorticoids (GCs) treat inflammatory skin diseases but cause atrophy.
- Glucocorticoid receptor (GR) mediates GC effects.
- REDD1, a GR target gene, is implicated in GC-induced skin atrophy.
Purpose of the Study:
- Investigate REDD1's role in GR function and signaling.
- Determine REDD1's impact on GC response in keratinocytes.
- Explore REDD1's potential in developing safer GC therapies.
Main Methods:
- Utilized HaCaT REDD1 knockout (KO) keratinocytes.
- Analyzed transcriptomic differences between REDD1 KO and control cells.
- Assessed GR activation, nuclear import, phosphorylation, and chaperone complex composition.
Main Results:
- REDD1 KO cells showed significantly reduced scope and amplitude of response to fluocinolone acetonide (FA).
- REDD1 status did not affect GR stability or key activation steps (nuclear import, Ser211 phosphorylation).
- Increased GR phosphorylation at Ser226 and abnormal nuclear translocation of FKBP51 were observed in REDD1 KO cells.
Conclusions:
- Results suggest a feed-forward loop in GR signaling mediated by REDD1.
- REDD1 influences GR nuclear import and transcriptional activity via chaperone complex modulation.
- Findings have translational potential for developing safer GR-targeted therapies for skin diseases.
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