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Inhibition Of Protein Translocation At The Endoplasmic Reticulum Promotes Activation Of The Unfolded Protein Response, Craig Mckibbin, Alina Mares, Michela Piacenti, Helen Williams, Peristera Roboti, Marjo Puumalainen, Anna Callan, Karolina Lesiak-Mieczkowska, Stig Linder, Hanna Harant, Stephen High, Sabine Flitsch, Roger Whitehead, Eileithyia Swanton
Inhibition Of Protein Translocation At The Endoplasmic Reticulum Promotes Activation Of The Unfolded Protein Response, Craig Mckibbin, Alina Mares, Michela Piacenti, Helen Williams, Peristera Roboti, Marjo Puumalainen, Anna Callan, Karolina Lesiak-Mieczkowska, Stig Linder, Hanna Harant, Stephen High, Sabine Flitsch, Roger Whitehead, Eileithyia Swanton
Research outputs 2012
Selective small-molecule inhibitors represent powerful tools for the dissection of complex biological processes. ESI (eeyarestatin I) is a novel modulator of ER (endoplasmic reticulum) function. In the present study, we show that in addition to acutely inhibiting ERAD (ER-associated degradation), ESI causes production of mislocalized polypeptides that are ubiquitinated and degraded. Unexpectedly, our results suggest that these non-translocated polypeptides promote activation of the UPR (unfolded protein response), and indeed we can recapitulate UPR activation with an alternative and quite distinct inhibitor of ER translocation. These results suggest that the accumulation of non-translocated proteins in the cytosol may represent a novel …