The ability to ensure proteostasis is critical for maintaining proper cell function and organismal viability but is mitigated by aging. We analyzed the role of the endoplasmic reticulum unfolded protein response (UPR(ER)) in aging of C. elegans and found that age-onset loss of ER proteostasis could be reversed by expression of a constitutively active form of XBP-1, XBP-1s. Neuronally derived XB...

The unfolded protein response (UPR) counteracts stress caused by unprocessed ER client proteins. A genome-wide survey showed impaired induction of many UPR target genes in xbp-1 mutant Caenorhabditis elegans that are unable to signal in the highly conserved IRE1-dependent UPR pathway. However a family of genes, abu (activated in blocked UPR), was induced to higher levels in ER-stressed xbp-1 mu...

Stresses that perturb the folding of nascent endoplasmic reticulum (ER) proteins activate the ER stress response. Upon ER stress, ER-associated ATF6 is cleaved; the resulting active cytosolic fragment of ATF6 translocates to the nucleus, binds to ER stress response elements (ERSEs), and induces genes, including the ER-targeted chaperone, GRP78. Recent studies showed that nutrient and oxygen sta...

Mammalian transcription factor ATF6 is constitutively synthesized as a type II transmembrane protein embedded in the endoplasmic reticulum (ER). Upon ER stress ATF6 is transported to the Golgi apparatus where it is cleaved to release its cytoplasmic domain. This is then translocated into the nucleus where it activates transcription of ER-localized molecular chaperones and folding enzymes to mai...

Mammalian transcription factor ATF6 is constitutively synthesized as a type II transmembrane protein embedded in the endoplasmic reticulum (ER). It is activated when unfolded proteins are accumulated in the ER under ER stress through a process called regulated intramembrane proteolysis (Rip), in which ATF6 is transported from the ER to the Golgi apparatus where it undergoes sequential cleavage ...

Parkin and DJ-1 are two multi-functional proteins linked to autosomal recessive early-onset Parkinson's disease (PD) that were shown to functionally interact by yet unknown mechanisms. We have delineated the mechanisms by which parkin controls DJ-1. Thus, parkin modulates DJ-1 transcription and protein levels via a signaling cascade involving p53 and the endoplasmic reticulum (ER)-stress-induce...

We have reported that the recombinant avirulent Newcastle disease virus (NDV) LaSota strain expressing the rabies virus glycoprotein (rL-RVG) could induce autophagy and apoptosis in gastric carcinoma cells. In the present study, we explored the upstream regulators, endoplasmic reticulum (ER) stress that induce autophagy and apoptosis and the relationships among them. For this purpose, SGC-7901 ...

اهتفاقثو اهرخفو ةملأا ةيأ ةيوه نم أزجتي لا اءزج يرامعملا ثارتلا لكشي . ةيخيراتلا ةرامعلا رصانع نا يف اهؤانبو اهميمصت مت دق ةيملاسلإا تابلطتمل يويحو لاعف لكشب ةباجتسلاا ىلع ةرداق نوكت ثيحب يضاملا ةينيدلاو ةيسفنلاو ةيعامتجلااو ةيئيبلاو ةيداملا سانلا . رضاحلا تقولا يف نويرامعملا نوسدنهملا موقي رصانعلا ذخأب اوذخأي ام ةداعو ميمصتلا عيراشم يف اهلاخدا و ةيملاسلإا ةيخيراتلا ينابملا نم ةفلتخملا نيوكت ر...

Adaptation to endoplasmic reticulum (ER) stress depends on the activation of the unfolded protein response (UPR) stress sensor inositol-requiring enzyme 1α (IRE1α), which functions as an endoribonuclease that splices the mRNA of the transcription factor XBP-1 (X-box-binding protein-1). Through a global proteomic approach we identified the BCL-2 family member PUMA as a novel IRE1α interactor. Im...