GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:24378737

From GONUTS
Jump to: navigation, search
Citation

Han, DH, Lee, YJ, Kim, K, Kim, CJ and Cho, S (2014) Modulation of glucocorticoid receptor induction properties by core circadian clock proteins. Mol. Cell. Endocrinol. 383:170-80

Abstract

Glucocorticoid (GC) plays important roles in diverse physiological processes including metabolism and immune functions. While circadian control of GC synthesis and secretion is relatively well appreciated, circadian control of GC action within target tissues remains poorly understood. Here, we demonstrate that CLOCK/BMAL1, the core circadian clock components, reduces maximal GR transactivation (A(max)) as well as efficacy (EC₅₀) by a novel mechanism that requires binding to DNA and transactivation of target genes. Accordingly, we observe that PER1 and CRY1, the primary targets of CLOCK/BMAL1 action, reduce maximal GR transactivation while not affecting the efficacy. Moreover, we observe hyper-activations of GRE-dependent transcription in BMAL1- or PERs-deficient MEFs. In addition, endogenous GC target genes expression negatively correlates with the CLOCK/BMAL1 activity. Considering that GC sensitivity is widely implicated in human health and diseases, these results provide valuable insights into plethora of GC-related physiology and pathology.

Links

PubMed Online version:10.1016/j.mce.2013.12.013

Keywords

ARNTL Transcription Factors/genetics; ARNTL Transcription Factors/metabolism; Animals; CLOCK Proteins/genetics; CLOCK Proteins/metabolism; Circadian Clocks/drug effects; Circadian Clocks/genetics; Cryptochromes/genetics; Cryptochromes/metabolism; DNA/metabolism; Dexamethasone/pharmacology; Gene Expression; Gene Expression Regulation; Genes, Reporter; Glucocorticoids/pharmacology; Luciferases/genetics; Luciferases/metabolism; Male; Mice; NIH 3T3 Cells; Period Circadian Proteins/genetics; Period Circadian Proteins/metabolism; Photoperiod; Protein Binding; Receptors, Glucocorticoid/genetics; Receptors, Glucocorticoid/metabolism; Signal Transduction; Transcriptional Activation/drug effects

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PER1

involved_in

GO:2000323: negative regulation of glucocorticoid receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CRY1

involved_in

GO:2000323: negative regulation of glucocorticoid receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CLOCK

involved_in

GO:2000323: negative regulation of glucocorticoid receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CLOCK

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BMAL1

involved_in

GO:2000323: negative regulation of glucocorticoid receptor signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BMAL1

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

See Help:References for how to manage references in GONUTS.