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

Research output: Contribution to journalJournal articleResearchpeer-review

Malin Hernebring, Asa Fredriksson, Maria Liljevald, Marija Cvijovic, Karin Norrman, John Wiseman, Tor Henrik Semb, Thomas Nyström

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 PA28aß (11S), subunits of the immunoproteasome (20Si), and the 20Si regulator TNFa. This induction is accompanied by assembly of mature PA28-20S(i) proteasomes and elevated proteasome activity. Inhibiting accumulation of PA28a using miRNA counteracted the removal of damaged proteins demonstrating that PA28aß has a hitherto unidentified role required for resetting the levels of protein damage at the transition from self-renewal to cell differentiation.
Original languageEnglish
JournalScientific Reports
Volume3
Pages (from-to)1381
Number of pages6
ISSN2045-2322
DOIs
Publication statusPublished - 5 Mar 2013

ID: 44739796