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

Sushil Devkota, Hyobin Jeong, Yunmi Kim, Muhammad Ali, Jae Il Roh, Daehee Hwang, Han Woong Lee

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2038-2053
Number of pages16
JournalAutophagy
Volume12
Issue number11
DOIs
Publication statusPublished - 2016 Nov 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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