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

• 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.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

MICE

IMMUNOPROTEASOME

SYSTEM

INDUCTION

GENE-EXPRESSION

SENESCENCE

OXIDATIVE-STRESS

INTERFERON-GAMMA

EMBRYONIC STEM-CELLS

NF-KAPPA-B

EMBRYONIC STEM-CELLS; NF-KAPPA-B; OXIDATIVE-STRESS; INTERFERON-GAMMA; GENE-EXPRESSION; IMMUNOPROTEASOME; MICE; SYSTEM; SENESCENCE; INDUCTION

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