Overexpression of CHOP in Myelinating Cells Does Not Confer a Significant Phenotype under Normal or Metabolic Stress Conditions

Abstract

Herein, we tackle the biggest controversy in the UPR literature: the function of the transcription factor CHOP as a protective or a prodeath factor. This manuscript is timely in light of the 2014 Lasker award for the UPR. Our in vivo data show that CHOP is not a prodeath protein, and we demonstrate that myelinating glial cells function normally in the presence of high CHOP expression from development to adulthood. Further, we propose a simplified view of UPR-mediated cell death after CHOP induction. We anticipate our work may turn the tide of the dogmatic view of CHOP and cause a reinvestigation of its function in different cell types. Accordingly, we believe our work will be a watershed for the UPR field.