Raw mediates antagonism of AP-1 activity in Drosophila.
High baselines of transcription factor activities represent fundamental obstacles to regulated signaling. Here we show that in Drosophila, quenching of basal activator protein 1 (AP-1) transcription factor activity serves as a prerequisite to its tight spatial and temporal control by the JNK (Jun N-terminal kinase) signaling cascade. Our studies indicate that the novel raw gene product is required to limit AP-1 activity to leading edge epidermal cells during embryonic dorsal closure. In addition, we provide the first evidence that the epidermis has a Basket JNK-independent capacity to activate AP-1 targets and that raw function is required broadly throughout the epidermis to antagonize this activity. Finally, our mechanistic studies of the three dorsal-open group genes [raw, ribbon (rib), and puckered (puc)] indicate that these gene products provide at least two tiers of JNK/AP-1 regulation. In addition to Puckered phosphatase function in leading edge epidermal cells as a negative-feedback regulator of JNK signaling, the three dorsal-open group gene products (Raw, Ribbon, and Puckered) are required more broadly in the dorsolateral epidermis to quench a basal, signaling-independent activity of the AP-1 transcription factor.
Bates
Katherine L
KL
Department of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA.
Higley
Matthew
M
Letsou
Anthea
A
D000483:Alleles; D000818:Animals; D019521:Body Patterning; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000378:metabolism; D004817:Epidermis / Q000196:embryology / Q000201:enzymology; D004843:Epistasis, Genetic; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D017344:Genes, Insect; D034582:Integumentary System / Q000196:embryology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008018:Life Cycle Stages; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009928:Organ Specificity; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D018808:Transcription Factor AP-1; C064196:dpp protein, Drosophila; C115863:raw protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; C110854:puc protein, Drosophila; D010749:Phosphoprotein Phosphatases