[Endoplasmic reticulum stress: light my fIRE].
Upon accumulation of misfolded proteins in the lumen of the endoplasmic reticulum (ER), a specific adaptive response, named the Unfolded Protein Response (UPR) is activated in order to protect cells from this stress. In metazoans, the UPR is mediated by three transmembrane ER resident proteins: PERK, ATF6 and IRE1. Among these, only IRE1 is found to be conserved from yeasts to mammals. IRE1 is a type I transmembrane protein which bears two enzymatic activities serine/threonine kinase and endoribonuclease. Crystal structures of S. cerevisiae luminal and cytosolic domains allowed a better understanding of its activation mode. However, IRE1 regulatory mechanisms and IRE1-dependent signalling pathways still remain to be fully explored. This review will present current knowledge on IRE1 protein and focus on its roles in physiological and pathophysiological processes.
Avenir Inserm U889, Université Bordeaux 2, 146, rue Léo Saignat, 33076 Bordeaux, France.
Marion
M
Bouchecareilh
Eric
E
Chevet
D002470:Cell Survival; D004721:Endoplasmic Reticulum / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D035941:Iron Regulatory Protein 1 / Q000235:genetics / Q000378:metabolism; D035925:Iron-Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology / Q000503:physiopathology; D011485:Protein Binding; D011489:Protein Denaturation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D035925:Iron-Regulatory Proteins; D029701:Saccharomyces cerevisiae Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D048848:MAP Kinase Kinase Kinase 5; D035941:Iron Regulatory Protein 1