LRH-1/NR5A2 interacts with the glucocorticoid receptor to regulate glucocorticoid resistance.
NR5A2
T cell acute lymphoblastic leukemia
apoptosis
glucocorticoid receptor
liver receptor homolog-1 (LRH-1)
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
05 09 2022
05 09 2022
Historique:
revised:
09
06
2022
received:
20
10
2021
accepted:
14
06
2022
pubmed:
9
7
2022
medline:
9
9
2022
entrez:
8
7
2022
Statut:
ppublish
Résumé
Nuclear receptors are transcription factors with important functions in a variety of physiological and pathological processes. Targeting glucocorticoid receptor (GR) activity using glucocorticoids is a cornerstone in the treatment of patients with T cell acute lymphoblastic leukemia (T-ALL), and resistance to GC-induced cell death is associated with poor outcome and a high risk for relapse. Next to ligand-binding, heterodimerization with other transcription factors presents an important mechanism for the regulation of GR activity. Here, we describe a GC-induced direct association of the Liver Receptor Homolog-1 (LRH-1) with the GR in the nucleus, which results in reciprocal inhibition of transcriptional activity. Pharmacological and molecular interference with LRH-1 impairs proliferation and survival in T-ALL and causes a profound sensitization to GC-induced cell death, even in GC-resistant T-ALL. Our data illustrate that direct interaction between GR and LRH-1 critically regulates glucocorticoid sensitivity in T-ALL opening up new perspectives for developing innovative therapeutic approaches to treat GC-resistant T-ALL.
Identifiants
pubmed: 35801407
doi: 10.15252/embr.202154195
pmc: PMC9442305
doi:
Substances chimiques
Glucocorticoids
0
NR5A2 protein, human
0
Receptors, Cytoplasmic and Nuclear
0
Receptors, Glucocorticoid
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e54195Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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