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

Malin Hernebring; Asa Fredriksson; Maria Liljevald; Marija Cvijovic; Karin Norrman; John Wiseman; Tor Henrik Semb; Thomas Nyström

doi:10.1038/srep01381

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

Malin Hernebring, Asa Fredriksson, Maria Liljevald, Marija Cvijovic, Karin Norrman, John Wiseman, Tor Henrik Semb, Thomas Nyström

Human Stem Cell Biology

38 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Scientific Reports
Vol/bind	3
Sider (fra-til)	1381
Antal sider	6
ISSN	2045-2322
DOI	https://doi.org/10.1038/srep01381
Status	Udgivet - 5 mar. 2013

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10.1038/srep01381

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587881/pdf/srep01381.pdf

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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.",

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author = "Malin Hernebring and Asa Fredriksson and Maria Liljevald and Marija Cvijovic and Karin Norrman and John Wiseman and Semb, {Tor Henrik} and Thomas Nystr{\"o}m",

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T1 - Removal of damaged proteins during ES cell fate specification requires the proteasome activator PA28

AU - Hernebring, Malin

AU - Fredriksson, Asa

AU - Liljevald, Maria

AU - Cvijovic, Marija

AU - Norrman, Karin

AU - Wiseman, John

AU - Semb, Tor Henrik

AU - Nyström, Thomas

PY - 2013/3/5

Y1 - 2013/3/5

N2 - 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.

AB - 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.

KW - Faculty of Health and Medical Sciences

KW - Embryonic Stem Cells

KW - PROTEIN QUALITY control

KW - STEM-CELL DIFFERENTIATION

KW - PROTEASOME

U2 - 10.1038/srep01381

DO - 10.1038/srep01381

M3 - Journal article

C2 - 23459332

SN - 2045-2322

VL - 3

SP - 1381

JO - Scientific Reports

JF - Scientific Reports

ER -

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

Abstract

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