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

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 PA28?? (11S), subunits of the immunoproteasome (20Si), and the 20Si regulator TNF?. This induction is accompanied by assembly of mature PA28-20S(i) proteasomes and elevated proteasome activity. Inhibiting accumulation of PA28? using miRNA counteracted the removal of damaged proteins demonstrating that PA28?? has a hitherto unidentified role required for resetting the levels of protein damage at the transition from self-renewal to cell differentiation.

SUBMITTER: Hernebring M

PROVIDER: S-EPMC3587881 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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

Hernebring Malin M Fredriksson Åsa Å Liljevald Maria M Cvijovic Marija M Norrman Karin K Wiseman John J Semb Henrik H Nyström Thomas T

Scientific reports 20130101

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. Inhibit ...[more]

PMID: 23459332

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