Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28

Research output: Contribution to journalArticle

Abstract

In embryonic stem cells, removal of oxidatively damaged proteins is triggered upon the first signs of cell fate specification but the underlying mechanism is not known. Here, we report that this phase of differentiation encompasses an unexpected induction of genes encoding the proteasome activator PA28 alpha beta (11S), subunits of the immunoproteasome (20Si), and the 20Si regulator TNF alpha. This induction is accompanied by assembly of mature PA28-20S(i) proteasomes and elevated proteasome activity. Inhibiting accumulation of PA28 alpha using miRNA counteracted the removal of damaged proteins demonstrating that PA28 alpha beta has a hitherto unidentified role required for resetting the levels of protein damage at the transition from self-renewal to cell differentiation.

Details

Authors
  • Malin Hernebring
  • Asa Fredriksson
  • Maria Liljevald
  • Marija Cvijovic
  • Karin Norrman
  • John Wiseman
  • Henrik Semb
  • Thomas Nystrom
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Article number1381
JournalScientific Reports
Volume3
Publication statusPublished - 2013
Publication categoryResearch
Peer-reviewedYes