Kenji Kohno

..Furthermore, recombinant fragments of subregion IV exhibited a self-binding ability. Therefore, although its sequence is little conserved evolutionarily, subregion IV plays an essential role to promote Ire1 dimer formation...

..In the first step, BiP dissociation from Ire1 leads to its cluster formation. In the second step, direct interaction of unfolded proteins with the CSSR orients the cytosolic effector domains of clustered Ire1 molecules...

..Here, we show by both in vivo and in vitro analyses that the RNase domain of IRE1 determines the functional specificities of each of these isoforms...

..This review focuses on current progress with efforts to elucidate how stress sensors recognize the accumulation of unfolded proteins...

..These novel DT receptors should be useful for the generation of transgenic mice by TRECK...

..Higher eukaryotes have evolved two other sensors, PERK and ATF6. This review focuses on the current progress in our understanding of stress-sensing mechanisms, in particular, the similarities and differences between yeast and mammals...

..In addition, their dependency on Rot1 appeared different. We therefore propose that Rot1 is a general chaperone with some substrate specificity...

..We therefore conclude that the cytosolic (or transmembrane) domain of Ire1 senses membrane aberrancy, while, as proposed previously, unfolded proteins accumulating in the ER interact with and activate Ire1...

..These observations indicate that in addition to BiP dissociation and self-association of Ire1, another unknown change on the luminal side is crucial for Ire1 activation...

..This system serves to enhance cytoplasmic splicing and could facilitate a more rapid response to ER stress, and represents a unique way of cotranslational protein targeting coupled to mRNA maturation...

..Thus, translational pausing may be used for unexpectedly diverse cellular processes in mammalian cells...

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..Moreover, we categorized 15 genes as those down-regulated by the UPR, most of which seem to encode cell surface or extracellular proteins. This UPR-mediated gene repression may alleviate the load of client proteins targeted to the ER...

..We conclude that in the ER stress-sensory system BiP is not the principal determinant of Ire1 activity, but an adjustor for sensitivity to various stresses...

..This implies that the protein folding machinery in which Rot1p is involved chaperones proteins acting in various physiological processes including cell wall synthesis and lysis of autophagic bodies...

..We speculate that recognition of unfolded proteins is based on their competition with Ire1 for binding with BiP/Kar2...

..Therefore we propose that the period of the somite segmentation clock is sensitive to Notch activity and that Nrarp plays essential roles in the morphology of vertebrae and ribs...

..We found that the transcription of some genes depends on functions possessed by both Tih2p and TBP and that these functions are substantially impaired in the spt15/tih2-ts160 double mutants that confer synthetic growth defects...

..These findings suggest that the activation of the UPR affects ER-to-Golgi transport via stimulation of COPII vesicle formation from the ER...

..Mutation of the ROT1 gene caused defects in cell wall synthesis and lysis of autophagic bodies. We suggest that Rot1 is required for folding of proteins engaged in these cellular processes...

..Compared with DNAJB12 mRNA that was widely expressed in mouse tissues, DNAJB14 mRNA was expressed more weakly, being most abundant in testis, implying its specific role in this tissue...

..These studies reveal the utility of the assay system and the unique properties of the mammalian cytosolic enzyme that can promote the splicing of XBP1u mRNA...

..Conversely, knockdown of DNAJB12 expression attenuated the degradation of CFTR. Thus, DNAJB12 is a novel mammalian ER-localized J-protein that plays a vital role in the quality control of membrane proteins...

..On the other hand, the K51E/E148K DT mutant exhibited no detectable cytotoxicity. This led us to successfully obtain DT gene transgenic mice, which exhibited no histological abnormalities, and indeed acquired immune tolerance to DT...

..We speculate that for the folding of some proteins in the ER, chaperoning by BiP and formation of proper disulfide bonds may synchronously occur in a JPDI-dependent manner...

..This study is a first step in elucidating the relationship between lipid metabolism and the ER stress response...

..These properties may account for the different responses observed under different conditions in mammalian cells, which carry multiple ER-stress sensors...

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..These findings raise the possibility that epigenetic status in transplanted NSCs can be manipulated to provide effective treatment for SCI...

..We conclude that Nse1p and the SMC5-SMC6 heterodimer together form a high molecular mass complex that is conserved in eukaryotes and required for both DNA repair and proliferation...

..When produced in bacteria as a fusion protein, the C-terminal region of OsIre1 showed autophosphorylation activity. These results thus indicate that OsIre1 encodes a putative plant transducer of ER stress...

..These results indicate that macrophages play a protective role in noninflammatory lung injury caused by the selective ablation of AE2 cells...

..This study describes the effects of HB-EGF on liver regeneration after 70% partial hepatectomy in proHB-EGF transgenic mice with liver-specific expression. Methods &..

..In addition, our present results suggest that ERAI transgenic mice are very useful for evaluating in vivo ER stress, especially in the liver, during the development of insulin resistance...

..These data validate the hypothesis that OMP-DTR mice can be used as a tool to ablate the mature olfactory sensory neurons in a controlled fashion and to study the regulatory mechanisms of the neuronal replacement...

..This model system provides strong support for the concept that podocyte depletion could be a major mechanism driving glomerulosclerosis and progressive loss of renal function in human glomerular diseases...

..We used transgenic animals expressing the ER stress indicator to show that it can be used to monitor physiological and pathological ER stress in vivo...