Proteasome response to interferon-γ is altered in senescent human fibroblasts

• Published in: FEBS letters 2006-07, Vol.580 (16), p.3989-3994
• Main Authors: Stratford, Fiona L.L., Chondrogianni, Niki, Trougakos, Ioannis P., Gonos, Efstathios S., Rivett, A. Jennifer
• Format: Article
• Language: English
• Subjects: 7-amido-4-methylcoumarin; AMC; Cells, Cultured; Cellular Senescence - physiology; chymotrypsin-like; CPD; CT-L; cumulative population doublings; Fibroblasts - cytology; Fibroblasts - drug effects; Human fibroblasts; Humans; IFN-γ; Immunoproteasome; Interferon-gamma - pharmacology; Interferon-γ; peptidyl-glutamyl peptide hydrolase; PGPH; Proteasome Endopeptidase Complex - immunology; Proteasome Endopeptidase Complex - metabolism; Proteasome expression; Protein Subunits - metabolism; Protein Transport; Replicative senescence; T-L; trypsin-like
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2006.06.029

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-γ (IFN-γ) was lost in senescent cells. In contrast, levels of the 11S proteasome regulator, PA28, were increased by IFN-γ 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.