Eukaryotic cells can adapt to endoplasmic reticulum (ER) dysfunction by producing diverse signals from the ER to the cytosol or nucleus. These signaling pathways are collectively known as the unfolded protein response (UPR). The canonical branches of the UPR are mediated by three ER membrane-bound proteins: double-stranded RNA-dependent protein kinase (PKR)-like endoplasmic reticulum kinase (PE...

The eIF2 kinase PERK and the integrated stress response facilitate activation of ATF6 during endoplasmic reticulum stress. Running title: The ISR facilitates activation of ATF6 Brian F. Teske, Sheree A. Wek, Piyawan Bunpo, Judy K. Cundiff, Jeanette N. McClintick, Tracy G. Anthony, and Ronald C. Wek Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianap...

Tick-borne encephalitis (TBE) is a serious human neurological disease caused by TBE virus (TBEV). However, the mechanisms of TBEV-caused pathogenesis remain unclear. The endoplasmic reticulum (ER) stress response, also defined as the unfolded protein response (UPR), is an important conserved molecular signaling pathway that modulates many biological functions including innate immunity and viral...

PURPOSE To investigate the anti-apoptotic mechanism of leptin in non-small cell lung cancer. MATERIALS AND METHODS The influences of leptin on apoptosis were investigated, analyzing the mechanism that triggers growth of A549 cells. The effects of leptin on cell proliferation were examined by XTT analysis. Leptin, C/EBP homologous protein (CHOP), phosphorylated-PKR-like ER kinase (p-Perk), ino...

RATIONALE Stresses, such as ischemia, impair folding of nascent proteins in the rough endoplasmic reticulum (ER), activating the unfolded protein response, which restores efficient ER protein folding, thus leading to protection from stress. In part, the unfolded protein response alleviates ER stress and cell death by increasing the degradation of terminally misfolded ER proteins via ER-associat...

Activating transcription factor 6 (ATF6) is located within the region of linkage to type 2 diabetes on chromosome 1q21-q23 and is a key activator of the endoplasmic reticulum stress response. We evaluated 78 single nucleotide polymorphisms (SNPs) spanning >213 kb in 95 people, from which we selected 64 SNPs for evaluation in 191 Caucasian case subjects from Utah and between 165 and 188 control ...

It is well known that the endoplasmic reticulum (ER) is capable of expanding its surface area in response both to cargo load and to increased expression of resident membrane proteins. Although the response to increased cargo load, known as the unfolded protein response (UPR), is well characterized, the mechanism of the response to membrane protein load has been unclear. As a model system to inv...

The purpose of this study was to determine, whether previously reported ethanol-induced alterations to the smooth endoplasmic reticulum (SER), predispose Purkinje neurons (PN) to thapsigargin-induced endoplasmic reticulum (ER) stress. Thapsigargin blocks the sarco/endoplasmic Ca(2+) ATPase pump (SERCA 2), depleting the SER of calcium. Forty-one, eight month old Fischer 344 male rats were treate...