Differential roles of proteasome and immunoproteasome regulators Pa28αβ, Pa28γ and Pa200 in the degradation of oxidized proteins

Andrew M Pickering, Kelvin J.A. Davies

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

The response and functions of proteasome regulators Pa28αβ (or 11S), Pa28γ and Pa200 in oxidative-stress adaptation (also called hormesis) was studied in murine embryonic fibroblasts (MEFs), using a well-characterized model of cellular adaptation to low concentrations (1.0-10.0 μM) of hydrogen peroxide (H 2O 2), which alter gene expression profiles, increasing resistance to higher levels of oxidative-stress. Pa28αβ bound to 20S proteasomes immediately upon H 2O 2-treatment, whereas 26S proteasomes were disassembled at the same time. Over the next 24 h, the levels of Pa28αβ, Pa28γ and Pa200 proteasome regulators increased during H 2O 2-adaptation, whereas the 19S regulator was unchanged. Purified Pa28αβ, and to a lesser extent Pa28γ, significantly increased the ability of purified 20S proteasome to selectively degrade oxidized proteins; Pa28αβ also increased the capacity of purified immunoproteasome to selectively degrade oxidized proteins but Pa28γ did not. Pa200 regulator actually decreased 20S proteasome and immunoproteasome's ability to degrade oxidized proteins but Pa200 and poly-ADP ribose polymerase may cooperate in enabling initiation of DNA repair. Our results indicate that cytoplasmic Pa28αβ and nuclear Pa28γ may both be important regulators of proteasome's ability to degrade oxidatively-damaged proteins, and induced-expression of both 20S proteasome and immunoproteasome, and their Pa28αβ and Pa28γ regulators are important for oxidative-stress adaptation.

Original languageEnglish (US)
Pages (from-to)181-190
Number of pages10
JournalArchives of Biochemistry and Biophysics
Volume523
Issue number2
DOIs
StatePublished - Jul 15 2012
Externally publishedYes

Fingerprint

Proteasome Endopeptidase Complex
Proteolysis
Degradation
Oxidative stress
Proteins
Oxidative Stress
Hormesis
Poly(ADP-ribose) Polymerases
Fibroblasts
Transcriptome
Gene expression
DNA Repair
Hydrogen Peroxide
Repair
DNA

Keywords

  • Immunoproteasome
  • Oxidative stress adaptation (hormesis)
  • Pa28 (11S) regulator
  • Proteasome regulators
  • Protein degradation
  • Ubiquitin-proteasome system

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

@article{2a4daf5c2ab94b8aa35402fb8d0cadfe,
title = "Differential roles of proteasome and immunoproteasome regulators Pa28αβ, Pa28γ and Pa200 in the degradation of oxidized proteins",
abstract = "The response and functions of proteasome regulators Pa28αβ (or 11S), Pa28γ and Pa200 in oxidative-stress adaptation (also called hormesis) was studied in murine embryonic fibroblasts (MEFs), using a well-characterized model of cellular adaptation to low concentrations (1.0-10.0 μM) of hydrogen peroxide (H 2O 2), which alter gene expression profiles, increasing resistance to higher levels of oxidative-stress. Pa28αβ bound to 20S proteasomes immediately upon H 2O 2-treatment, whereas 26S proteasomes were disassembled at the same time. Over the next 24 h, the levels of Pa28αβ, Pa28γ and Pa200 proteasome regulators increased during H 2O 2-adaptation, whereas the 19S regulator was unchanged. Purified Pa28αβ, and to a lesser extent Pa28γ, significantly increased the ability of purified 20S proteasome to selectively degrade oxidized proteins; Pa28αβ also increased the capacity of purified immunoproteasome to selectively degrade oxidized proteins but Pa28γ did not. Pa200 regulator actually decreased 20S proteasome and immunoproteasome's ability to degrade oxidized proteins but Pa200 and poly-ADP ribose polymerase may cooperate in enabling initiation of DNA repair. Our results indicate that cytoplasmic Pa28αβ and nuclear Pa28γ may both be important regulators of proteasome's ability to degrade oxidatively-damaged proteins, and induced-expression of both 20S proteasome and immunoproteasome, and their Pa28αβ and Pa28γ regulators are important for oxidative-stress adaptation.",
keywords = "Immunoproteasome, Oxidative stress adaptation (hormesis), Pa28 (11S) regulator, Proteasome regulators, Protein degradation, Ubiquitin-proteasome system",
author = "Pickering, {Andrew M} and Davies, {Kelvin J.A.}",
year = "2012",
month = "7",
day = "15",
doi = "10.1016/j.abb.2012.04.018",
language = "English (US)",
volume = "523",
pages = "181--190",
journal = "Archives of Biochemistry and Biophysics",
issn = "0003-9861",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Differential roles of proteasome and immunoproteasome regulators Pa28αβ, Pa28γ and Pa200 in the degradation of oxidized proteins

AU - Pickering, Andrew M

AU - Davies, Kelvin J.A.

PY - 2012/7/15

Y1 - 2012/7/15

N2 - The response and functions of proteasome regulators Pa28αβ (or 11S), Pa28γ and Pa200 in oxidative-stress adaptation (also called hormesis) was studied in murine embryonic fibroblasts (MEFs), using a well-characterized model of cellular adaptation to low concentrations (1.0-10.0 μM) of hydrogen peroxide (H 2O 2), which alter gene expression profiles, increasing resistance to higher levels of oxidative-stress. Pa28αβ bound to 20S proteasomes immediately upon H 2O 2-treatment, whereas 26S proteasomes were disassembled at the same time. Over the next 24 h, the levels of Pa28αβ, Pa28γ and Pa200 proteasome regulators increased during H 2O 2-adaptation, whereas the 19S regulator was unchanged. Purified Pa28αβ, and to a lesser extent Pa28γ, significantly increased the ability of purified 20S proteasome to selectively degrade oxidized proteins; Pa28αβ also increased the capacity of purified immunoproteasome to selectively degrade oxidized proteins but Pa28γ did not. Pa200 regulator actually decreased 20S proteasome and immunoproteasome's ability to degrade oxidized proteins but Pa200 and poly-ADP ribose polymerase may cooperate in enabling initiation of DNA repair. Our results indicate that cytoplasmic Pa28αβ and nuclear Pa28γ may both be important regulators of proteasome's ability to degrade oxidatively-damaged proteins, and induced-expression of both 20S proteasome and immunoproteasome, and their Pa28αβ and Pa28γ regulators are important for oxidative-stress adaptation.

AB - The response and functions of proteasome regulators Pa28αβ (or 11S), Pa28γ and Pa200 in oxidative-stress adaptation (also called hormesis) was studied in murine embryonic fibroblasts (MEFs), using a well-characterized model of cellular adaptation to low concentrations (1.0-10.0 μM) of hydrogen peroxide (H 2O 2), which alter gene expression profiles, increasing resistance to higher levels of oxidative-stress. Pa28αβ bound to 20S proteasomes immediately upon H 2O 2-treatment, whereas 26S proteasomes were disassembled at the same time. Over the next 24 h, the levels of Pa28αβ, Pa28γ and Pa200 proteasome regulators increased during H 2O 2-adaptation, whereas the 19S regulator was unchanged. Purified Pa28αβ, and to a lesser extent Pa28γ, significantly increased the ability of purified 20S proteasome to selectively degrade oxidized proteins; Pa28αβ also increased the capacity of purified immunoproteasome to selectively degrade oxidized proteins but Pa28γ did not. Pa200 regulator actually decreased 20S proteasome and immunoproteasome's ability to degrade oxidized proteins but Pa200 and poly-ADP ribose polymerase may cooperate in enabling initiation of DNA repair. Our results indicate that cytoplasmic Pa28αβ and nuclear Pa28γ may both be important regulators of proteasome's ability to degrade oxidatively-damaged proteins, and induced-expression of both 20S proteasome and immunoproteasome, and their Pa28αβ and Pa28γ regulators are important for oxidative-stress adaptation.

KW - Immunoproteasome

KW - Oxidative stress adaptation (hormesis)

KW - Pa28 (11S) regulator

KW - Proteasome regulators

KW - Protein degradation

KW - Ubiquitin-proteasome system

UR - http://www.scopus.com/inward/record.url?scp=84861869794&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861869794&partnerID=8YFLogxK

U2 - 10.1016/j.abb.2012.04.018

DO - 10.1016/j.abb.2012.04.018

M3 - Article

VL - 523

SP - 181

EP - 190

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

IS - 2

ER -