Down-regulation of transcription factor CF2 by Drosophila Ras/MAP kinase signaling in oogenesis: cytoplasmic retention and degradation.
Dorsoventral (D/V) patterning in Drosophila oogenesis is initiated by the transmission of a TGF-alpha-like ligand, Gurken (Grk), from the oocyte to the anterodorsal follicle cells, activating the EGF receptor (Egfr) signaling pathway. The zinc-finger transcription factor CF2 is a negative regulator of the rhomboid (rho) gene that encodes an essential membrane-bound component of the dorsalizing pathway. Expression of CF2 itself is negatively regulated by the activated Egfr. In this report, we demonstrate that CF2 is the target of down-regulation by the MAPK kinase cascade, and that this down-regulation is independent of the Rho function. These results suggest that D/V patterning involves a two-step signaling process: the initial Egfr signal, which represses CF2 and induces rho expression; and the subsequent Egfr + Rho signal, which determines the dorsal cell fates. Furthermore, we show that CF2 down-regulation occurs at the post-translational level through a mechanism involving coupled cytoplasmic retention and degradation.
Mantrova
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Center for Molecular and Structural Biology and Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Hsu
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D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D020929:Mitogen-Activated Protein Kinase Kinases; D009866:Oogenesis; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers; D018631:ras Proteins / Q000235:genetics*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; C076904:Cf2 protein, Drosophila; D011494:Protein Kinases; D019908:Proto-Oncogene Proteins c-raf; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins