Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28
Journal article, 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
Author
Malin Hernebring
University of Gothenburg
Åsa Fredriksson
University of Gothenburg
M. Liljevald
AstraZeneca AB
Marija Cvijovic
University of Gothenburg
Chalmers, Mathematical Sciences, Mathematics
K. Norrman
Lund University
J. Wiseman
AstraZeneca AB
Henrik Semb
University of Copenhagen
Lund University
Thomas Nyström
University of Gothenburg
Scientific Reports
2045-2322 (ISSN) 20452322 (eISSN)
Vol. 3 3 artikel nr 1381- 1381Subject Categories
Biological Sciences
DOI
10.1038/srep01381