Journal
SCIENTIFIC REPORTS
Volume 3, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep01381
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Funding
- Swedish Natural Research Council (VR)
- Knut and Alice Wallenberg Foundation
- Advanced ERC grant (QualiAge)
- EC (Acronym: Proteomage)
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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.
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