The SCFSlimb E3 ligase complex regulates asymmetric division to inhibit neuroblast overgrowth |
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| Authors: | Song Li Cheng Wang Edwin Sandanaraj Sherry S Y Aw Chwee T Koe Jack J L Wong Fengwei Yu Beng T Ang Carol Tang Hongyan Wang |
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| Institution: | 1. Neuroscience & Behavioral Disorders Program, Duke‐National University of Singapore Graduate Medical School Singapore, Singapore City, Singapore;2. NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore City, Singapore;3. Singapore Institute for Clinical Sciences, A*STAR, Singapore City, Singapore;4. National Neuroscience Institute, Singapore City, Singapore;5. Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, Singapore City, Singapore;6. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore;7. Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore City, Singapore |
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| Abstract: | Drosophila larval brain neuroblasts divide asymmetrically to balance between self‐renewal and differentiation. Here, we demonstrate that the SCFSlimb 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. |
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| Keywords: | asymmetric division neuroblasts polarity the SCF complex |
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