Cell 1990,
PMID: 2169352
Yang-Yen, H F; Chambard, J C; Sun, Y L; Smeal, T; Schmidt, T J; Drouin, J; Karin, M
Glucocorticoids are potent inhibitors of collagenase induction by phorbol esters and inflammatory mediators. The target for this negative effect is the AP-1 site within the collagenase promoter, which also mediates its induction. Negative regulation is due to repression of AP-1 activity by the glucocorticoid receptor (GCR). While the GCR is a potent inhibitor of AP-1 activity (Jun/Fos), both c-Jun and c-Fos are potent repressors of GCR activity. In vitro experiments using purified GCR and c-Jun proteins suggest that mutual repression is due to direct interaction between the two. Direct interaction between GCR and either c-Jun or c-Fos is demonstrated by cross-linking and coimmunoprecipitation. These findings reveal a cross talk between two major signal transduction systems used to control gene transcription in response to extracellular stimuli, and a novel mechanism for transcriptional repression.
Document information provided by NCBI PubMed
Text Mining Data
Dashed line = No text mining data
Manually curated Databases
-
NCI Pathway Database Glucocorticoid receptor regulatory network:
JUN/FOS complex (FOS-JUN)
→
cortisol/GR alpha (monomer)/JUN/FOS complex (NR3C1-FOS-JUN)
(transcription, activates)
Evidence: mutant phenotype, reporter gene, physical interaction
-
NCI Pathway Database AP-1 transcription factor network:
JUN/FOS/GR/TRIP6/cortisol/GR alpha (dimer) complex (FOS-JUN-TRIP6-NR3C1)
→
JUN/FOS/TRIP6 complex (FOS-JUN-TRIP6)
(transcription, inhibits)
Evidence: mutant phenotype, reporter gene, physical interaction
-
NCI Pathway Database Glucocorticoid receptor regulatory network:
cortisol/GR alpha (monomer) complex (NR3C1)
→
JUN/FOS complex (FOS-JUN)
(modification, collaborate)
Evidence: mutant phenotype, reporter gene, physical interaction
-
NCI Pathway Database Glucocorticoid receptor regulatory network:
cortisol/GR alpha (monomer) complex (NR3C1)
→
cortisol/GR alpha (monomer)/JUN/FOS complex (NR3C1-FOS-JUN)
(modification, collaborate)
Evidence: mutant phenotype, reporter gene, physical interaction
-
NCI Pathway Database Glucocorticoid receptor regulatory network:
JUN/FOS complex (FOS-JUN)
→
cortisol/GR alpha (monomer)/JUN/FOS complex (NR3C1-FOS-JUN)
(modification, collaborate)
Evidence: mutant phenotype, reporter gene, physical interaction
In total, 10 gene pairs are associated to this article in curated databases