Ionizing radiation affects 26s proteasome function and associated molecular responses, even at low doses

Radiother Oncol. 2001 May;59(2):203-12. doi: 10.1016/s0167-8140(01)00311-5.


Background and purpose: Ionizing radiation is known to activate certain signal transduction pathways, the regulation of which could involve post-transcriptional as well as transcriptional mechanisms. One of the most important post-transcriptional pathways in eukaryotic cells is the ATP- and ubiquitin-dependent degradation of proteins by the 26s proteasome. This process controls initiation of many cellular stress responses, as well as inflammatory responses under control of the transcription factor NF-kappaB. The literature on the relationship between radiation and inflammation seems somewhat paradoxical. At high doses, radiation is generally pro-inflammatory. On the other hand, low dose radiation has a long history of use in the treatment of inflammatory disease. This suggests the involvement of multiple mechanisms that may operate differentially at different dose levels.

Materials and methods: In this paper, the ability of different doses of ionizing radiation to directly affect 26s proteasome activity was tested in ECV 304 cells. Proteasome activity, IkappaBalpha protein levels, and NF-kappaB activation were monitored.

Results: Inhibition of chymotrypsin-like 20s and 26s proteasome activity was observed immediately after low- and high-dose irradiation either of cells or purified proteasomes. The inhibitory effect was independent of the availability of the known endogenous proteasome inhibitor heat shock protein 90 (hsp90). Levels of IkappaBalpha, a physiological 26s proteasome substrate, were increased only at low doses (0.25 Gy) and unaltered at higher doses whereas only the highest doses (8 and 20 Gy) activated NF-kappaB.

Conclusions: We conclude that the proteasome is a direct target of ionizing radiation and suggest that inhibition of proteasome function provides a molecular framework within which low dose anti-inflammatory effects of radiation, and radiation-induced molecular responses in general, should be considered.

MeSH terms

  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / radiation effects
  • Humans
  • I-kappa B Proteins*
  • Inflammation / metabolism*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • NF-kappa B / radiation effects
  • Peptide Hydrolases / radiation effects*
  • Proteasome Endopeptidase Complex*
  • Radiation, Ionizing*


  • DNA-Binding Proteins
  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • NF-KappaB Inhibitor alpha
  • Peptide Hydrolases
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease