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

Malin Hernebring ; Åsa Fredriksson ; M. Liljevald ; Marija Cvijovic (Institutionen för matematiska vetenskaper) ; K. Norrman ; J. Wiseman ; Henrik Semb ; Thomas Nyström
Scientific Reports (2045-2322). 3, p. artikel nr 1381. (2013)
[Artikel, refereegranskad vetenskaplig]

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.

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



Denna post skapades 2013-04-02. Senast ändrad 2013-04-24.
CPL Pubid: 175205

 

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Institutionen för matematiska vetenskaperInstitutionen för matematiska vetenskaper (GU)

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