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Functional characterization of EI24-induced autophagy in the degradation of RING-domain E3 ligases
- Functional characterization of EI24-induced autophagy in the degradation of RING-domain E3 ligases
- 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
- Autophagy, 12(11), 2038-2053
- Article Type
- Autophagy; Bioenergy; Computational Biology; E3 Ligase; EI24; Ei24 Protein; Female; Genetic Transfection; Genotoxicity; Hela Cell Line; Human; Human Cell; Human Cell Culture; Immunocytochemistry; Mammalian Target of Rapamycin; Membrane Protein; Proteasome; Protein Analysis; Protein Binding; Protein Degradation; Protein MDM2; Protein P53; Regulatory Mechanism; Ring-Domain; Ring Finger Motif; Signal Transduction; Trim41 Protein; Tumor Necrosis Factor Receptor Associated Factor2; Ubiquitin Protein Ligase E3; Unclassified Drug
- 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.
- Taylor and Francis Inc.
- Related Researcher
Hwang, Dae Hee
Systems Biology and Medicine Lab
Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
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