To independently confirm and extend these results, we analyzed a different downstream target of the ire-1-xbp-1 pathway. Using proteomics, we identified a protein, Y41C4A.11 (a homolog of the beta-prime subunit of the coatomer complex), that increased 4.6 fold in C. elegans animals exposed to Cry5B and whose increase was completely dependent on xbp-1 (see Materials and Methods and Protocol S1). The gene encoding this protein was previously demonstrated to be transcriptionally regulated by tunicamycin in an ire-1 and xbp-1 dependent manner [12] . Using real time PCR, we find that both hsp-4 mRNA and Y41C4A.11 mRNA are induced by either Cry5B or tunicamycin ( Figure 5F ). Consistent with activation of the ire-1-xbp-1 pathway by p38 MAPK in response to PFT but not unfolded proteins, the full induction of both mRNAs by Cry5B, but not tunicamycin, is dependent on sek-1 MAPKK. Interestingly, whereas induction of both mRNAs by Cry5B is lacking in xbp-1(zc12) mutant animals (confirming that activation of hsp-4 and Y41C4A.11 by PFT is via the UPR), both mRNAs are still somewhat induced by Cry5B in a sek-1(km4) mutant, albeit at lower levels than in wild-type animals. These data suggest that some of the UPR-mediated transcriptional response is p38 pathway independent.