Transrepression of AP-1 by nuclear receptors in Drosophila.
Mammalian cell culture studies have shown that several members of the nuclear receptor super family such as glucocorticoid receptor, retinoic acid receptor and thyroid hormone receptor can repress the activity of AP-1 proteins by a mechanism that does not require the nuclear receptor to bind to DNA directly, but that is otherwise poorly understood. Several aspects of nuclear receptor function are believed to rely on this inhibitory mechanism, which is referred to as transrepression. This study presents evidence that nuclear receptor-mediated transrepression of AP-1 occurs in Drosophila melanogaster. In two different developmental situations, embryonic dorsal closure and wing development, several nuclear receptors, including Seven up, Tailless, and Eagle antagonize AP-1. The inhibitory interactions with nuclear receptors are integrated with other modes of AP-1 regulation, such as mitogen-activated protein kinase signaling. A potential role of nuclear receptors in setting a threshold of AP-1 activity required for the manifestation of a cellular response is discussed.
Gritzan
Uwe
U
European Molecular Biology Laboratory, Meyerhofstr. 1, 69117 Heidelberg, Germany.
Weiss
Carsten
C
Brennecke
Julius
J
Bohmann
Dirk
D
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D009479:Neuropeptides / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009479:Neuropeptides; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D012097:Repressor Proteins; C074090:TLL protein, Drosophila; D018808:Transcription Factor AP-1; C098694:eg protein, Drosophila; C435749:kay protein, Drosophila; C094295:svp protein, Drosophila; D008156:Luciferases