Induction of cellular stress responses by celastrol. (A) Illustration showing key aspects of the unfolded protein response (UPR) and heat shock response (HSR), both of which have been reported to be induced by celastrol (Mu et al. 2008; Trott et al. 2008). Expected transcriptional targets are shown inside the nucleus, with targets of HSF1, the key transcription factor (TF) activated in the HSR, in red, and targets of the TFs associated with the three major branches of the UPR—XBP1, ATF4, and ATF6—in green, purple, and blue, respectively. Asterisks indicate genes that were differentially expressed in our experiments with FDR ≤ 0.01. (B) PRO-seq-based log fold changes in expression in K562 cells after 160 min of treatment by celastrol for numerous known targets of the same four TFs: XBP1, ATF4, ATF6, and HSF1. Genes labeled are the same as those listed in A. Only targets of HSF1 display strong up-regulation.
