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Sci Rep. 2013;3:1381. doi: 10.1038/srep01381.

Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28.

Author information

1
Department of Chemistry and Molecular Biology, University of Gothenburg, SE-413 90 Göteborg, Sweden. malin.hernebring@med.lu.se

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.

PMID:
23459332
PMCID:
PMC3587881
DOI:
10.1038/srep01381
[Indexed for MEDLINE]
Free PMC Article

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