| First Author | Homma T | Year | 2016 |
| Journal | Exp Cell Res | Volume | 349 |
| Issue | 1 | Pages | 128-138 |
| PubMed ID | 27743894 | Mgi Jnum | J:260895 |
| Mgi Id | MGI:6152026 | Doi | 10.1016/j.yexcr.2016.10.006 |
| Citation | Homma T, et al. (2016) Heat stress promotes the down-regulation of IRE1alpha in cells: An atypical modulation of the UPR pathway. Exp Cell Res 349(1):128-138 |
| abstractText | Heat stress induces intracellular protein denaturation and endoplasmic reticulum (ER) stress, which elicits unfolded protein response (UPR) in cells. UPR involves three ER-localized sensor proteins: the inositol-requiring protein 1alpha (IRE1alpha), the dsRNA-activated protein kinase-like ER kinase (PERK), and activating transcription factor-6 (ATF6). However, the precise mechanism by which cells deal with heat stress remains to be elucidated. We report herein that heat stress effectively activates all branches of the UPR. While splicing of the XBP-1 mRNA is usually triggered by activated IRE1alpha, the level of this protein was found to be decreased immediately after the occurrence of heat stress and the down-regulation gradually recovered thereafter. The protein levels of other UPR sensors or ER luminal proteins were unaffected. The down-regulation of IRE1alpha was independent of cellular viability. It thus appears that the heat-stress induced down-regulation of the IRE1alpha protein may lead to the termination of the IRE1alpha signaling pathway in an attempt to avoid excessive responses. We investigated the machinery causing IRE1alpha down-regulation and found that heat stress effectively promoted the activation of autophagy. Importantly, the inhibition of either proteasomes or autophagic flux failed to rescue the loss of IRE1alpha following heat stress. These collective results suggest that heat stress simultaneously activates both the UPR and autophagy, followed by the activation of a negative feedback system in UPR by modulating the responses related to the IRE1alpha-XBP-1 axis. |
