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

Köbenhavns Universitet

Lund University

Thomas Nyström

University of Gothenburg

Scientific Reports

2045-2322 (ISSN)

3 artikel nr 1381- 1381

Subject Categories

Biological Sciences

DOI

10.1038/srep01381

More information

Latest update

5/8/2018 1