title: Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28.
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 PA28αβ (11S), subunits of the immunoproteasome (20Si), and the 20Si regulator TNFα. This induction is accompanied by assembly of mature PA28-20S(i) proteasomes and elevated proteasome activity. Inhibiting accumulation of PA28α using miRNA counteracted the removal of damaged proteins demonstrating that PA28αβ has a hitherto unidentified role required for resetting the levels of protein damage at the transition from self-renewal to cell differentiation.
authors: Department of Chemistry and Molecular Biology, University of Gothenburg, SE-413 90 Göteborg, Sweden. malin.hernebring@med.lu.se
authors: Malin
authors: M
authors: Hernebring
authors: Åsa
authors: Å
authors: Fredriksson
authors: Maria
authors: M
authors: Liljevald
authors: Marija
authors: M
authors: Cvijovic
authors: Karin
authors: K
authors: Norrman
authors: John
authors: J
authors: Wiseman
authors: Henrik
authors: H
authors: Semb
authors: Thomas
authors: T
authors: Nyström
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D050050:Protein Carbonylation; D021122:Protein Subunits / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D011506:Proteins; D046988:Proteasome Endopeptidase Complex; C486213:Psme1 protein, mouse