Negative regulation of Jun/AP-1: conserved function of glycogen synthase kinase 3 and the Drosophila kinase shaggy.
Transcription factor AP-1 is constituted by the products of the various fos and jun genes. AP-1 activity is modulated by second messengers and appears to involve post-translational modifications of Fos and Jun. It has been shown that phosphorylation mediated by glycogen synthase kinase 3 (GSK-3) is involved in negative regulation of c-Jun DNA-binding function in vitro. Here we show that two forms of GSK-3 function to decrease the DNA-binding activity as well as the transcriptional activation elicited by c-Jun in vivo. Similarly, the other members of the jun family, JunB, JunD and v-Jun, are negatively regulated by GSK-3 in vivo, although to a slightly lesser extent than c-Jun. We have also tested the proteins encoded by the Drosophila shaggy gene (sgg) in our assays. The sgg proteins share homology with the mammalian GSK-3 and appear to be important for the normal segregation of bristle precursor cells in the imaginal epithelium in Drosophila. Here we show that the products of the sgg gene can also function as negative regulators of Jun/AP-1.
Laboratoire de Génétique Moléculaire des Eucaryotes de CNRS, Unité 184 de l'INSERM, Faculté de Médecine, Strasbourg, France.
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RP
de Groot
J
J
Auwerx
M
M
Bourouis
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P
Sassone-Corsi
D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000201:enzymology*; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D011494:Protein Kinases; D038341:Glycogen Synthase Kinases; C080335:Sgg protein, Drosophila; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3