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 SCFSlimb 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. Synopsis This report provides evidence that loss of the SCFSlimb E3 ubiquitin ligase complex as well as hyperactivation of Akt lead to neuroblast overgrowth and defects in asymmetric cell division. Slimb, the F-box protein of the SCF complex, associates with Akt in a protein complex, and SCFSlimb acts through SAK and Akt to inhibit neuroblast overgrowth. The SCFSlimb E3 ubiquitin ligase inhibits neuroblast (NB) overgrowth and regulates asymmetric division of NBs. The NB overgrowth phenotype in the absence of SCFS limb is similar to what is seen in conditions of AKT hyperactivation. The F-box protein Slimb associates with AKT and regulates NB overgrowth via SAK and AKT. This report provides evidence that loss of the SCFSlimb E3 ubiquitin ligase complex as well as hyperactivation of Akt lead to neuroblast overgrowth and defects in asymmetric cell division. Slimb, the F-box protein of the SCF complex, associates with Akt in a protein complex, and SCF Slimb acts through SAK and Akt to inhibit neuroblast overgrowth. © 2014 The Authors.