Cited 1 time in webofscience Cited 2 time in scopus

Functional characterization of EI24-induced autophagy in the degradation of RING-domain E3 ligases

Title
Functional characterization of EI24-induced autophagy in the degradation of RING-domain E3 ligases
Authors
Devkota, S[Devkota, Sushil]Jeong, H[Jeong, Hyobin]Kim, Y[Kim, Yunmi]Ali, M[Ali, Muhammad]Roh, JI[Roh, Jae-il]Hwang, D[Hwang, Daehee]Lee, HW[Lee, Han-Woong]
DGIST Authors
Jeong, H[Jeong, Hyobin]; Hwang, D[Hwang, Daehee]
Issue Date
2016
Citation
Autophagy, 12(11), 2038-2053
Type
Article
Article Type
Article
Keywords
AutophagyBioenergyComputational BiologyE3 LigaseEI24Ei24 ProteinFemaleGenetic TransfectionGenotoxicityHela Cell LineHumanHuman CellHuman Cell CultureImmunocytochemistryMammalian Target of RapamycinMembrane ProteinProteasomeProtein AnalysisProtein BindingProtein DegradationProtein MDM2Protein P53Regulatory MechanismRing-DomainRing Finger MotifSignal TransductionTrim41 ProteinTumor Necrosis Factor Receptor Associated Factor2Ubiquitin Protein Ligase E3Unclassified Drug
ISSN
1554-8627
Abstract
Historically, the ubiquitin-proteasome system (UPS) and autophagy pathways were believed to be independent; however, recent data indicate that these pathways engage in crosstalk. To date, the players mediating this crosstalk have been elusive. Here, we show experimentally that EI24 (EI24, autophagy associated transmembrane protein), a key component of basal macroautophagy/autophagy, degrades 14 physiologically important E3 ligases with a RING (really interesting new gene) domain, whereas 5 other ligases were not degraded. Based on the degradation results, we built a statistical model that predicts the RING E3 ligases targeted by EI24 using partial least squares discriminant analysis. Of 381 RING E3 ligases examined computationally, our model predicted 161 EI24 targets. Those targets are primarily involved in transcription, proteolysis, cellular bioenergetics, and apoptosis and regulated by TP53 and MTOR signaling. Collectively, our work demonstrates that EI24 is an essential player in UPS-autophagy crosstalk via degradation of RING E3 ligases. These results indicate a paradigm shift regarding the fate of E3 ligases. © 2016 Sushil Devkota, Hyobin Jeong, Yunmi Kim, Muhammad Ali, Jae-il Roh, Daehee Hwang, and Han-Woong Lee. Published with license by Taylor & Francis.
URI
http://hdl.handle.net/20.500.11750/2778
DOI
10.1080/15548627.2016.1217371
Publisher
Taylor and Francis Inc.
Related Researcher
  • Author Hwang, Dae Hee Systems Biology and Medicine Lab
  • Research Interests Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
Files:
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Collection:
New BiologyETC1. Journal Articles


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