Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28
Artikel i vetenskaplig tidskrift, 2013
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.
MICE
IMMUNOPROTEASOME
SYSTEM
INDUCTION
GENE-EXPRESSION
SENESCENCE
OXIDATIVE-STRESS
INTERFERON-GAMMA
EMBRYONIC STEM-CELLS
NF-KAPPA-B
Författare
Malin Hernebring
Göteborgs universitet
Åsa Fredriksson
Göteborgs universitet
M. Liljevald
AstraZeneca AB
Marija Cvijovic
Göteborgs universitet
Chalmers, Matematiska vetenskaper, Matematik
K. Norrman
Lunds universitet
J. Wiseman
AstraZeneca AB
Henrik Semb
Köpenhamns universitet
Lunds universitet
Thomas Nyström
Göteborgs universitet
Scientific Reports
2045-2322 (ISSN)
Vol. 3 3 artikel nr 1381- 1381Ämneskategorier
Biologiska vetenskaper
DOI
10.1038/srep01381