We aimed to investigate the contribution of co-translational protein aggregation to
the chemotherapy resistance of tumor cells. Increased co-translational protein aggregation
reflects altered translation regulation that may have the potential to buffer transcription
under genotoxic stress. As an indicator for such an event, we followed the cytoplasmic
aggregation of RPB1, the aggregation-prone largest subunit of RNA polymerase II, in
biopsy samples taken from patients with invasive carcinoma of no special type. RPB1
frequently aggregates co-translationally in the absence of proper HSP90 chaperone
function or in ribosome mutant cells as revealed formerly in yeast. We found that
cytoplasmic foci of RPB1 occur in larger sizes in tumors that showed no regression
after therapy. Based on these results, we propose that monitoring the cytoplasmic
aggregation of RPB1 may be suitable for determining—from biopsy samples taken before
treatment—the effectiveness of neoadjuvant chemotherapy.
