ECPAS/Ecm29-mediated 26S proteasome disassembly is an adaptive response to glucose starvation

Won Hoon Choi, Yejin Yun, Insuk Byun, Sumin Kim, Seho Lee, Jiho Sim, Shahar Levi, Seo Hyeong Park, Jeongmoo Jun, Oded Kleifeld, Kwang Pyo Kim, Dohyun Han, Tomoki Chiba, Chaok Seok, Yong Tae Kwon, Michael H. Glickman, Min Jae Lee

Research output: Contribution to journalArticlepeer-review


The 26S proteasome comprises 20S catalytic and 19S regulatory complexes. Approximately half of the proteasomes in cells exist as free 20S complexes; however, our mechanistic understanding of what determines the ratio of 26S to 20S species remains incomplete. Here, we show that glucose starvation uncouples 26S holoenzymes into 20S and 19S subcomplexes. Subcomplex affinity purification and quantitative mass spectrometry reveal that Ecm29 proteasome adaptor and scaffold (ECPAS) mediates this structural remodeling. The loss of ECPAS abrogates 26S dissociation, reducing degradation of 20S proteasome substrates, including puromycylated polypeptides. In silico modeling suggests that ECPAS conformational changes commence the disassembly process. ECPAS is also essential for endoplasmic reticulum stress response and cell survival during glucose starvation. In vivo xenograft model analysis reveals elevated 20S proteasome levels in glucose-deprived tumors. Our results demonstrate that the 20S-19S disassembly is a mechanism adapting global proteolysis to physiological needs and countering proteotoxic stress.

Original languageEnglish
Article number112701
JournalCell Reports
Issue number7
StatePublished - 25 Jul 2023


  • 19S complex
  • 20S proteasome
  • CP: Metabolism
  • Ecm29
  • disassembly
  • glucose
  • in silico modeling
  • proteasome
  • proteolysis
  • starvation

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology


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