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 LaB

38 Citations (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.

Original language	English
Journal	Scientific Reports
Volume	3
Pages (from-to)	1381
Number of pages	6
ISSN	2045-2322
DOIs	https://doi.org/10.1038/srep01381
Publication status	Published - 5 Mar 2013

Keywords

Faculty of Health and Medical Sciences
Embryonic Stem Cells
PROTEIN QUALITY control
STEM-CELL DIFFERENTIATION
PROTEASOME

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10.1038/srep01381

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

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title = "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 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.",

keywords = "Faculty of Health and Medical Sciences, Embryonic Stem Cells, PROTEIN QUALITY control, STEM-CELL DIFFERENTIATION, PROTEASOME",

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",

year = "2013",

month = mar,

day = "5",

doi = "10.1038/srep01381",

language = "English",

volume = "3",

pages = "1381",

journal = "Scientific Reports",

issn = "2045-2322",

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TY - JOUR

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

Keywords

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