Mitofusin 2 (Mfn2) is a key protein in mitochondrial fusion and it participates in the bridging of mitochondria to the endoplasmic reticulum (ER). Recent data indicate that Mfn2 ablation leads to ER stress. Here we report on the mechanisms by which Mfn2 modulates cellular responses to ER stress. Induction of ER stress in Mfn2-deficient cells caused massive ER expansion and excessive activation ...

Activation of adaptive mechanisms plays a crucial role in cancer progression and drug resistance by allowing cell survival under stressful conditions. Therefore, inhibition of the adaptive response is considered as a prospective therapeutic strategy. The PERK-eIF2α phosphorylation pathway is an important arm of the unfolded protein response (UPR), which is induced under conditions of endoplasmi...

Input signals originating from baroreceptors and vestibular receptors are integrated in the rostral ventrolateral medulla (RVLM) to maintain blood pressure during postural movement. The contribution of baroreceptors and vestibular receptors in the maintenance of blood pressure following hypotension were quantitatively analyzed by measuring phosphorylated extracellular regulated protein kinase (...

We report the first detailed examination of the brain of a patient with Wolcott-Rallison syndrome. Wolcott-Rallison syndrome is an extremely rare clinical manifestation of a lack of protein kinase R-like endoplasmic reticulum kinase (PERK) function caused by mutations in the PERK gene EIF2AK3. Protein kinase R-like endoplasmic reticulum kinase is thought to play a significant pathogenetic role ...

Vanishing white matter disease (VWMD) is an inherited autosomal-recessive hypomyelinating disease caused by mutations in eukaryotic translation initiation factor 2B (eIF2B). eIF2B mutations predominantly affect the brain white matter, and the characteristic features of VWMD pathology include myelin loss and foamy oligodendrocytes. Activation of pancreatic endoplasmic reticulum kinase (PERK) has...

The protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) signaling pathway was reported to exert an important role in neuronal apoptosis. The present study was designed to investigate the roles of the PERK signaling pathway in the secondary brain injury (SBI) induced by intracerebral hemorrhage (ICH) and its potential mechanisms. Sprague-Dawley rats were used to establish ICH models ...

The unfolded protein response (UPR) is an evolutionarily conserved stress response to intra- and extracellular conditions that disrupt endoplasmic reticulum (ER) protein-folding capacity. The UPR is engaged by a variety of disease conditions, including most cancers as well as both metabolic and neurodegenerative disorders. Three transmembrane transducers-PERK, IRE1, and ATF6-are responsible for...

Abstract We study how firms build relations with local governments in emerging markets without established rules of political lobbying. document that following a turnover the Party Secretary or mayor city China, (especially privately owned enterprises, POEs hereafter) headquartered significantly increase their “perk spending,” for example, expenses travel and entertainment among others. Both in...

UNLABELLED Epithelial-to-mesenchymal transition (EMT) promotes both tumor progression and drug resistance, yet few vulnerabilities of this state have been identified. Using selective small molecules as cellular probes, we show that induction of EMT greatly sensitizes cells to agents that perturb endoplasmic reticulum (ER) function. This sensitivity to ER perturbations is caused by the synthesis...

Malignant carcinomas that recur following therapy are typically de-differentiated and multidrug resistant (MDR). De-differentiated cancer cells acquire MDR by up-regulating reactive oxygen species (ROS)-scavenging enzymes and drug efflux pumps, but how these genes are up-regulated in response to de-differentiation is not known. Here, we examine this question by using global transcriptional prof...