Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor.
We present evidence that the glucocorticoid receptor (GR) and transcription factor Jun/AP-1 can reciprocally repress one another's transcriptional activation by a novel mechanism that is independent of DNA binding. Overexpression of c-Jun prevents the glucocorticoid-induced activation of genes carrying a functional glucocorticoid response element (GRE). Conversely, GR is able to repress AP-1-mediated transcriptional activation. Mutant analysis reveals that the ligand binding and DNA binding domains of GR and the region including the leucine zipper of c-Jun are required for repression. Gel retardation analysis demonstrates that bacterially expressed c-Jun disrupts GR-GRE complexes. These data indicate that members of two distinct classes of transcription factors can oppose one another's activity through a mechanism likely involving protein-protein interactions.
Schüle
R
R
Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California 92037.
Rangarajan
P
P
Kliewer
S
S
Ransone
L J
LJ
Bolado
J
J
Yang
N
N
Verma
I M
IM
Evans
R M
RM
D000818:Animals; D002460:Cell Line; D002872:Chromosome Deletion; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D003012:Microbial Collagenase / Q000096:biosynthesis / Q000235:genetics; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000502:physiology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D004268:DNA-Binding Proteins; D016755:Proto-Oncogene Proteins c-jun; D011965:Receptors, Glucocorticoid; D012097:Repressor Proteins; D014157:Transcription Factors; D003907:Dexamethasone; D011505:Protein-Tyrosine Kinases; D003012:Microbial Collagenase