title: Dronc caspase exerts a non-apoptotic function to restrain phospho-Numb-induced ectopic neuroblast formation in Drosophila.
abstract: Drosophila neuroblasts have served as a model to understand how the balance of stem cell self-renewal versus differentiation is achieved. Drosophila Numb protein regulates this process through its preferential segregation into the differentiating daughter cell. How Numb restricts the proliferation and self-renewal potentials of the recipient cell remains enigmatic. Here, we show that phosphorylation at conserved sites regulates the tumor suppressor activity of Numb. Enforced expression of a phospho-mimetic form of Numb (Numb-TS4D) or genetic manipulation that boosts phospho-Numb levels, attenuates endogenous Numb activity and causes ectopic neuroblast formation (ENF). This effect on neuroblast homeostasis occurs only in the type II neuroblast lineage. We identify Dronc caspase as a novel binding partner of Numb, and demonstrate that overexpression of Dronc suppresses the effects of Numb-TS4D in a non-apoptotic and possibly non-catalytic manner. Reduction of Dronc activity facilitates ENF induced by phospho-Numb. Our findings uncover a molecular mechanism that regulates Numb activity and suggest a novel role for Dronc caspase in regulating neural stem cell homeostasis.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Yingshi
authors.initials: Y
authors.lastname: Ouyang
authors.forename: Claudia
authors.initials: C
authors.lastname: Petritsch
authors.forename: Hong
authors.initials: H
authors.lastname: Wen
authors.forename: Lily
authors.initials: L
authors.lastname: Jan
authors.forename: Yuh Nung
authors.initials: YN
authors.lastname: Jan
authors.forename: Bingwei
authors.initials: B
authors.lastname: Lu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D020169:Caspases / Q000096:biosynthesis / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology* / Q000502:physiology; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000378:metabolism*; D015870:Gene Expression; D057809:HEK293 Cells; D006706:Homeostasis; D006801:Humans; D020287:In Situ Nick-End Labeling; D007605:Juvenile Hormones / Q000096:biosynthesis / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D007605:Juvenile Hormones; C060606:numb protein, Drosophila; C072004:polo protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D020169:Caspases; C118731:dronc protein, Drosophila