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A Cullin1-Based SCF E3 Ubiquitin Ligase Targets the InR/PI3K/TOR Pathway to Regulate Neuronal Pruning
by
Li, Song
, Kirilly, Daniel
, Wu, Chunlai
, Yu, Fengwei
, Wang, Hongyan
, Liou, Yih-Cherng
, Wang, Cheng
, Wong, Jack Jing Lin
, Lim, Edwin Kok Hao
, Zhang, Heng
, Wang, Yan
in
Animals
/ Apoptosis
/ Calcium-Binding Proteins
/ Carrier Proteins - genetics
/ Carrier Proteins - metabolism
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ Cullin Proteins - genetics
/ Cullin Proteins - metabolism
/ Dendrites - metabolism
/ DNA-Binding Proteins - genetics
/ Drosophila - embryology
/ Drosophila - genetics
/ Drosophila - metabolism
/ Drosophila Proteins - genetics
/ Drosophila Proteins - metabolism
/ Ecdysone - metabolism
/ Gene Expression Regulation, Developmental
/ Insects
/ Kinases
/ Ligases
/ Metamorphosis, Biological
/ Mushroom Bodies - innervation
/ Nervous System - embryology
/ Neurons - metabolism
/ Neurophysiology
/ Nuclear Proteins
/ Phosphatidylinositol 3-Kinases - metabolism
/ Physiological aspects
/ Proteins
/ Proto-Oncogene Proteins c-akt - genetics
/ Proto-Oncogene Proteins c-akt - metabolism
/ Receptor Protein-Tyrosine Kinases - metabolism
/ RNA Interference
/ RNA, Small Interfering
/ SKP Cullin F-Box Protein Ligases - genetics
/ SKP Cullin F-Box Protein Ligases - metabolism
/ SOXB2 Transcription Factors - genetics
/ TOR Serine-Threonine Kinases - metabolism
/ Ubiquitin
/ Ubiquitin-Protein Ligases - genetics
/ Ubiquitin-Protein Ligases - metabolism
/ Ubiquitination
2013
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A Cullin1-Based SCF E3 Ubiquitin Ligase Targets the InR/PI3K/TOR Pathway to Regulate Neuronal Pruning
by
Li, Song
, Kirilly, Daniel
, Wu, Chunlai
, Yu, Fengwei
, Wang, Hongyan
, Liou, Yih-Cherng
, Wang, Cheng
, Wong, Jack Jing Lin
, Lim, Edwin Kok Hao
, Zhang, Heng
, Wang, Yan
in
Animals
/ Apoptosis
/ Calcium-Binding Proteins
/ Carrier Proteins - genetics
/ Carrier Proteins - metabolism
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ Cullin Proteins - genetics
/ Cullin Proteins - metabolism
/ Dendrites - metabolism
/ DNA-Binding Proteins - genetics
/ Drosophila - embryology
/ Drosophila - genetics
/ Drosophila - metabolism
/ Drosophila Proteins - genetics
/ Drosophila Proteins - metabolism
/ Ecdysone - metabolism
/ Gene Expression Regulation, Developmental
/ Insects
/ Kinases
/ Ligases
/ Metamorphosis, Biological
/ Mushroom Bodies - innervation
/ Nervous System - embryology
/ Neurons - metabolism
/ Neurophysiology
/ Nuclear Proteins
/ Phosphatidylinositol 3-Kinases - metabolism
/ Physiological aspects
/ Proteins
/ Proto-Oncogene Proteins c-akt - genetics
/ Proto-Oncogene Proteins c-akt - metabolism
/ Receptor Protein-Tyrosine Kinases - metabolism
/ RNA Interference
/ RNA, Small Interfering
/ SKP Cullin F-Box Protein Ligases - genetics
/ SKP Cullin F-Box Protein Ligases - metabolism
/ SOXB2 Transcription Factors - genetics
/ TOR Serine-Threonine Kinases - metabolism
/ Ubiquitin
/ Ubiquitin-Protein Ligases - genetics
/ Ubiquitin-Protein Ligases - metabolism
/ Ubiquitination
2013
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A Cullin1-Based SCF E3 Ubiquitin Ligase Targets the InR/PI3K/TOR Pathway to Regulate Neuronal Pruning
by
Li, Song
, Kirilly, Daniel
, Wu, Chunlai
, Yu, Fengwei
, Wang, Hongyan
, Liou, Yih-Cherng
, Wang, Cheng
, Wong, Jack Jing Lin
, Lim, Edwin Kok Hao
, Zhang, Heng
, Wang, Yan
in
Animals
/ Apoptosis
/ Calcium-Binding Proteins
/ Carrier Proteins - genetics
/ Carrier Proteins - metabolism
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ Cullin Proteins - genetics
/ Cullin Proteins - metabolism
/ Dendrites - metabolism
/ DNA-Binding Proteins - genetics
/ Drosophila - embryology
/ Drosophila - genetics
/ Drosophila - metabolism
/ Drosophila Proteins - genetics
/ Drosophila Proteins - metabolism
/ Ecdysone - metabolism
/ Gene Expression Regulation, Developmental
/ Insects
/ Kinases
/ Ligases
/ Metamorphosis, Biological
/ Mushroom Bodies - innervation
/ Nervous System - embryology
/ Neurons - metabolism
/ Neurophysiology
/ Nuclear Proteins
/ Phosphatidylinositol 3-Kinases - metabolism
/ Physiological aspects
/ Proteins
/ Proto-Oncogene Proteins c-akt - genetics
/ Proto-Oncogene Proteins c-akt - metabolism
/ Receptor Protein-Tyrosine Kinases - metabolism
/ RNA Interference
/ RNA, Small Interfering
/ SKP Cullin F-Box Protein Ligases - genetics
/ SKP Cullin F-Box Protein Ligases - metabolism
/ SOXB2 Transcription Factors - genetics
/ TOR Serine-Threonine Kinases - metabolism
/ Ubiquitin
/ Ubiquitin-Protein Ligases - genetics
/ Ubiquitin-Protein Ligases - metabolism
/ Ubiquitination
2013
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A Cullin1-Based SCF E3 Ubiquitin Ligase Targets the InR/PI3K/TOR Pathway to Regulate Neuronal Pruning
Journal Article
A Cullin1-Based SCF E3 Ubiquitin Ligase Targets the InR/PI3K/TOR Pathway to Regulate Neuronal Pruning
2013
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Overview
Pruning that selectively eliminates unnecessary axons/dendrites is crucial for sculpting the nervous system during development. During Drosophila metamorphosis, dendrite arborization neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone, whereas mushroom body γ neurons specifically eliminate their axon branches within dorsal and medial lobes. However, it is unknown which E3 ligase directs these two modes of pruning. Here, we identified a conserved SCF E3 ubiquitin ligase that plays a critical role in pruning of both ddaC dendrites and mushroom body γ axons. The SCF E3 ligase consists of four core components Cullin1/Roc1a/SkpA/Slimb and promotes ddaC dendrite pruning downstream of EcR-B1 and Sox14, but independently of Mical. Moreover, we demonstrate that the Cullin1-based E3 ligase facilitates ddaC dendrite pruning primarily through inactivation of the InR/PI3K/TOR pathway. We show that the F-box protein Slimb forms a complex with Akt, an activator of the InR/PI3K/TOR pathway, and promotes Akt ubiquitination. Activation of the InR/PI3K/TOR pathway is sufficient to inhibit ddaC dendrite pruning. Thus, our findings provide a novel link between the E3 ligase and the InR/PI3K/TOR pathway during dendrite pruning.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Carrier Proteins - metabolism
/ Cell Cycle Proteins - genetics
/ Cell Cycle Proteins - metabolism
/ Cullin Proteins - metabolism
/ DNA-Binding Proteins - genetics
/ Drosophila Proteins - genetics
/ Drosophila Proteins - metabolism
/ Gene Expression Regulation, Developmental
/ Insects
/ Kinases
/ Ligases
/ Mushroom Bodies - innervation
/ Phosphatidylinositol 3-Kinases - metabolism
/ Proteins
/ Proto-Oncogene Proteins c-akt - genetics
/ Proto-Oncogene Proteins c-akt - metabolism
/ Receptor Protein-Tyrosine Kinases - metabolism
/ SKP Cullin F-Box Protein Ligases - genetics
/ SKP Cullin F-Box Protein Ligases - metabolism
/ SOXB2 Transcription Factors - genetics
/ TOR Serine-Threonine Kinases - metabolism
/ Ubiquitin-Protein Ligases - genetics
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