biostudies-literatureDeichsel SDeutsche ForschungsgemeinschaftUniversität HohenheimNIH HHSRP89582https://www.ebi.ac.uk/biostudies/studies/S-EPMC11540305biostudies-literatureUnknown12Notch signalling activity regulates hematopoiesis in <i>Drosophila</i> and vertebrates alike. Parasitoid wasp infestation of <i>Drosophila</i> larvae, however, requires a timely downregulation of Notch activity to allow the formation of encapsulation-active blood cells. Here, we show that the <i>Drosophila</i> CSL transcription factor Suppressor of Hairless [Su(H)] is phosphorylated at Serine 269 in response to parasitoid wasp infestation. As this phosphorylation interferes with the DNA binding of Su(H), it reversibly precludes its activity. Accordingly, phospho-deficient <i>Su(H)^S269A</i> mutants are immune-compromised. A screen for kinases involved in Su(H) phosphorylation identified Pkc53E, required for normal hematopoiesis as well as for parasitoid immune response. Genetic aeLifeInhibition of the Notch signal transducer CSL by Pkc53E-mediated phosphorylation to fend off parasitic immune challenge in <i>Drosophila</i>.PMC11540305P40 OD010949P40 OD018537NA 427/5-1Deichsel SMastel HGahr BMFechner JNagel ACZimmermann MPreiss AFrankenreiter LPreis IfalseInhibition of the Notch signal transducer CSL by Pkc53E-mediated phosphorylation to fend off parasitic immune challenge in <i>Drosophila</i>.Notch signalling activity regulates hematopoiesis in <i>Drosophila</i> and vertebrates alike. Parasitoid wasp infestation of <i>Drosophila</i> larvae, however, requires a timely downregulation of Notch activity to allow the formation of encapsulation-active blood cells. Here, we show that the <i>Drosophila</i> CSL transcription factor Suppressor of Hairless [Su(H)] is phosphorylated at Serine 269 in response to parasitoid wasp infestation. As this phosphorylation interferes with the DNA binding of Su(H), it reversibly precludes its activity. Accordingly, phospho-deficient <i>Su(H)^S269A</i> mutants are immune-compromised. A screen for kinases involved in Su(H) phosphorylation identified Pkc53E, required for normal hematopoiesis as well as for parasitoid immune response. Genetic a2024-01-01T00:00:00Z2024 Nov2026-06-01T17:33:32.437Z2025-04-19T04:24:43.641ZS-EPMC115403053950373910.7554/eLife.89582