Proteasome response to interferon-gamma is altered in senescent human fibroblasts.
We have investigated immunoproteasomes in human fibroblasts during replicative senescence. Unlike levels of constitutive proteasome catalytic subunits and 26S proteasome regulatory subunits, levels of immunosubunits did not decrease dramatically in senescent cells. However, the induction of immunosubunits by interferon-gamma (IFN-gamma) was lost in senescent cells. In contrast, levels of the 11S proteasome regulator, PA28, were increased by IFN-gamma even in senescent cells, and both immunosubunits and PA28 increased with the reversible growth arrest in confluent cell cultures. The results highlight differences in the mechanisms of regulation of immunoproteasomes compared to constitutive proteasomes and in the irreversible growth arrest of senescent cells compared to reversible contact-induced growth arrest.
Stratford
Fiona L L
FL
Department of Biochemistry, University of Bristol, School of Medical Sciences, Bristol, BS8 1TD, United Kingdom.
Chondrogianni
Niki
N
Trougakos
Ioannis P
IP
Gonos
Efstathios S
ES
Rivett
A Jennifer
AJ
D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000276:immunology / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport
D021122:Protein Subunits; D007371:Interferon-gamma; D046988:Proteasome Endopeptidase Complex