Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28
Research output: Contribution to journal › Journal article › Research › peer-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.
|Number of pages||6|
|Publication status||Published - 5 Mar 2013|
- The Faculty of Health and Medical Sciences - Embryonic Stem Cells, PROTEIN QUALITY control, STEM-CELL DIFFERENTIATION, PROTEASOME