Evolution of the unfolded protein response in plants.

The unfolded protein response (UPR) in plants is elicited by endoplasmic reticulum stress, which can be brought about by adverse environmental conditions. The response is mediated by a conserved signalling network composed of two branches - one branch involving inositol requiring enzyme1- basic leucine zipper60 (IRE1-bZIP60) signalling pathway and another branch involving the membrane transcription factors, bZIP17 and -28. The UPR has been reported in Chlamydomonas reinhardtii, a unicellular green alga, which lacks some canonical UPR signalling components found in vascular plants, raising the question whether C. reinhardtii uses other means such as oxidative signalling or Regulated IRE1-Dependent Decay to activate the UPR. In vascular plants, IRE1 splices bZIP60 mRNA in response to endoplasmic reticulum stress by cutting at a site in the RNA that is highly conserved in structure and sequence. Monocots have a single IRE1 gene required for viability in rice, while dicots have two IRE1 genes, IRE1a and -b. Brassicas have a third IRE1 gene, IRE1c, which lacks a lumenal domain, but is required in combination with IRE1b for gametogenesis. Vascular and non-vascular plants upregulate a similar set of genes in response to endoplasmic reticulum stress despite differences in the complexity of their UPR signalling networks.

Dual role of Endoplasmic Reticulum Stress-Mediated Unfolded Protein Response Signaling Pathway in Carcinogenesis.

Cancer constitutes a grave problem nowadays in view of the fact that it has become one of the main causes of death worldwide. Poor clinical prognosis is presumably due to cancer cells metabolism as tumor microenvironment is affected by oxidative stress. This event triggers adequate cellular response and thereby creates appropriate conditions for further cancer progression. Endoplasmic reticulum (ER) stress occurs when the balance between an ability of the ER to fold and transfer proteins and the degradation of the misfolded ones become distorted. Since ER is an organelle relatively sensitive to oxidative damage, aforementioned conditions swiftly cause the activation of the unfolded protein response (UPR) signaling pathway. The output of the UPR, depending on numerous factors, may vary and switch between the pro-survival and the pro-apoptotic branch, and hence it displays opposing effects in deciding the fate of the cancer cell. The role of UPR-related proteins in tumorigenesis, such as binding the immunoglobulin protein (BiP) and inositol-requiring enzyme-1α (IRE1α), activating transcription factor 6 (ATF6) or the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), has already been specifically described so far. Nevertheless, due to the paradoxical outcomes of the UPR activation as well as gaps in current knowledge, it still needs to be further investigated. Herein we would like to elicit the actual link between neoplastic diseases and the UPR signaling pathway, considering its major branches and discussing its potential use in the development of a novel, anti-cancer, targeted therapy.