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

Köbenhavns Universitet

Lunds universitet

Thomas Nyström

Göteborgs universitet

Scientific Reports

2045-2322 (ISSN)

3 artikel nr 1381- 1381

Ämneskategorier

Biologiska vetenskaper

DOI

10.1038/srep01381

Mer information

Senast uppdaterat

2018-05-08