Imaging of radiation effects on cellular 26S proteasome function in situ.

Purpose: The classical radiobiological paradigm is that DNA is the target for cell damage caused by ionising radiation. However, evidence is accumulating that other constituents, such as the membrane, organelles, and proteins, are also important targets. We have shown that the isolated 26S proteasome is one such target and here we wish to substantiate it within the cell, in situ.

Epidermal growth factor receptor vIII expression in U87 glioblastoma cells alters their proteasome composition, function, and response to irradiation.

Little is known about the factors that influence the proteasome structures in cells and their activity, although this could be highly relevant to cancer therapy. We have previously shown that, within minutes, irradiation inhibits substrate degradation by the 26S proteasome in most cell types. Here, we report an exception in U87 glioblastoma cells transduced to express the epidermal growth factor receptor vIII (EGFRvIII) mutant (U87EGFRvIII), which does not respond to irradiation with 26S proteasome inhibition.