Compensatory regulation among ER chaperones in C. elegans.

We have identified a particularly clear case of compensatory transcriptional regulation among ER chaperones in Caenorhabditis elegans using a GFP reporter transgene that is under the control of the promoter of hsp-4, a C. elegans homolog of GRP-78/BiP. Knockdown by RNA interference of 9 known or predicted ER chaperones induced hsp-4 upregulation via the ire-1/xbp-1 signaling cascade employed in the unfolded protein response. We show that this compensatory regulation is specific for ER chaperones, not dependent on RNA interference, and required for maintaining viability in worms containing a deletion of the hsp-3 gene.