title: The SCFSlimb E3 ligase complex regulates asymmetric division to inhibit neuroblast overgrowth.
abstract: Drosophila larval brain neuroblasts divide asymmetrically to balance between self-renewal and differentiation. Here, we demonstrate that the SCF(Slimb) E3 ubiquitin ligase complex, which is composed of Cul1, SkpA, Roc1a and the F-box protein Supernumerary limbs (Slimb), inhibits ectopic neuroblast formation and regulates asymmetric division of neuroblasts. Hyperactivation of Akt leads to similar neuroblast overgrowth and defects in asymmetric division. Slimb associates with Akt in a protein complex, and SCF(S)(limb) acts through SAK and Akt to inhibit neuroblast overgrowth. Moreover, Beta-transducin repeat containing, the human ortholog of Slimb, is frequently deleted in highly aggressive gliomas, suggesting a conserved tumor suppressor-like function.
authors.affiliation: Neuroscience & Behavioral Disorders Program, Duke-National University of Singapore Graduate Medical School Singapore, Singapore City, Singapore.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Edwin
authors.initials: E
authors.lastname: Sandanaraj
authors.forename: Sherry S Y
authors.initials: SS
authors.lastname: Aw
authors.forename: Chwee T
authors.initials: CT
authors.lastname: Koe
authors.forename: Jack J L
authors.initials: JJ
authors.lastname: Wong
authors.forename: Fengwei
authors.initials: F
authors.lastname: Yu
authors.forename: Beng T
authors.initials: BT
authors.lastname: Ang
authors.forename: Carol
authors.initials: C
authors.lastname: Tang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015293:Transducin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C110233:slmb protein, Drosophila; D044767:Ubiquitin-Protein Ligases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C522064:Sak protein, Drosophila; D015293:Transducin