Figure 3. The positive feedback loop between MYC and IRE1α pathway.

In MYC‐hyperactivated tumors, IRE1α‐XBP1s signaling and MYC likely engage in a positive feedback loop, as XBP1s transcriptionally upregulates MYC while c‐Myc directly induces ERN1 (encoding IRE1α) and XBP1 expression. c‐Myc also physically interacts with XBP1s and enhances its transcriptional activity. MYC is further shown to contribute to IRE1α protein stability via unknown mechanisms (denoted as dashed line). Red arrows indicate direct transcriptional regulation between MYC and IRE1α arm.