Genomes and Genes
Affiliation: University of Michigan
- The unfolded protein response in nutrient sensing and differentiationRandal J Kaufman
Department of Biological Chemistry, University of Michigan Medical Center, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109 0650, USA
Nat Rev Mol Cell Biol 3:411-21. 2002....
- Activation of GCN2 in UV-irradiated cells inhibits translationJing Deng
Department of Biochemistry and McGill Cancer Centre, McGill University, 3655 Promenade Sir William Osler, Montreal, H3G 1Y6, Quebec, Canada
Curr Biol 12:1279-86. 2002..While the effects of UV irradiation on DNA replication and transcription have been extensively studied, the mechanism(s) responsible for translational repression are poorly understood...
- The unfolded protein response: a pathway that links insulin demand with beta-cell failure and diabetesDonalyn Scheuner
Department of Biological Chemistry, and Howard Hughes Medical Institute, The University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
Endocr Rev 29:317-33. 2008..Therapeutic interventions to prevent polypeptide-misfolding, oxidative damage, and/or UPR-induced cell death have the potential to improve beta-cell function and/or survival in the treatment of diabetes...
- Translation attenuation through eIF2alpha phosphorylation prevents oxidative stress and maintains the differentiated state in beta cellsSung Hoon Back
Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, MI 48109 0650, USA
Cell Metab 10:13-26. 2009..The finding that increased proinsulin synthesis causes oxidative damage in beta cells may reflect events in the beta cell failure associated with insulin resistance in type 2 diabetes...
- Control of mRNA translation preserves endoplasmic reticulum function in beta cells and maintains glucose homeostasisDonalyn Scheuner
Howard Hughes Medical Institute, University of Michigan, 1150 W Medical Center Drive, Ann Arbor, Michigan 48109, USA
Nat Med 11:757-64. 2005..We propose that translational control couples insulin synthesis with folding capacity to maintain ER integrity and that this signal is essential to prevent diet-induced type 2 diabetes...
- The unfolded protein response sensor IRE1alpha is required at 2 distinct steps in B cell lymphopoiesisKezhong Zhang
Department of Biological Chemistry and Howard Hughes Medical Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA
J Clin Invest 115:268-81. 2005..These results suggest specific requirements of the IRE1alpha-mediated UPR subpathway in the early and late stages of B lymphopoiesis...
- Double-stranded RNA-dependent protein kinase phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 mediates apoptosisDonalyn Scheuner
Department of Biological Chemistry, Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, 48109 0650, USA
J Biol Chem 281:21458-68. 2006..We propose that eIF2alpha phosphorylation is fundamentally a death signal, yet it may promote either death or survival, depending upon coincident signaling events...
- Ultraviolet light activates NFkappaB through translational inhibition of IkappaBalpha synthesisShiyong Wu
Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
J Biol Chem 279:34898-902. 2004..Based upon our results, we propose a novel mechanism by which UV light regulates early phase NFkappaB activation by means of an ER-stress-induced translational inhibition pathway...
- Chop deletion reduces oxidative stress, improves beta cell function, and promotes cell survival in multiple mouse models of diabetesBenbo Song
Howard Hughes Medical Institute and Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan, USA
J Clin Invest 118:3378-89. 2008..These findings suggest that CHOP is a fundamental factor that links protein misfolding in the ER to oxidative stress and apoptosis in beta cells under conditions of increased insulin demand...
- The double-stranded RNA-activated protein kinase mediates viral-induced encephalitisDonalyn Scheuner
Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109, USA
Virology 317:263-74. 2003..They support PKR to be an effective target to control tissue damage due to deleterious host responses to viral infection...
- A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stressMichael Boyce
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Science 307:935-9. 2005..More broadly, salubrinal demonstrates the feasibility of selective pharmacological targeting of cellular dephosphorylation events...
- Glucose activates a protein phosphatase-1-mediated signaling pathway to enhance overall translation in pancreatic beta-cellsDirk Vander Mierde
Gene Expression Unit, Department of Molecular Cell Biology, KU Leuven, Herestraat 49, B 3000 Leuven, Belgium
Endocrinology 148:609-17. 2007..Because defects in the pancreatic endoplasmic reticulum kinase-eIF2alpha signaling system lead to beta-cell failure and diabetes, deregulation of the PP1 system could likewise lead to cellular dysfunction and disease...
- Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 is required for activation of NF-kappaB in response to diverse cellular stressesHao Yuan Jiang
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
Mol Cell Biol 23:5651-63. 2003..The absence of NF-kappaB-mediated transcription and its antiapoptotic function provides an explanation for why eIF2alpha kinase deficiency in diseases such as Wolcott-Rallison syndrome leads to cellular apoptosis and disease...
- Bioactive small molecules reveal antagonism between the integrated stress response and sterol-regulated gene expressionHeather P Harding
Skirball Institute of Biomolecular Medicine, New York University, New York, New York 10016, USA
Cell Metab 2:361-71. 2005..These findings suggest a mechanism by which interactions between sterol metabolism, the ISR, and the SREBP pathway affect lipid metabolism during ER stress...
- ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growthMeixia Bi
Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
EMBO J 24:3470-81. 2005..Collectively, these findings demonstrate that activation of the ISR is required for tumor cell adaptation to hypoxia, and suggest that this pathway is an attractive target for antitumor modalities...
- Stress granules and processing bodies are dynamically linked sites of mRNP remodelingNancy Kedersha
Division of Rheumatology and Immunology, Harvard Medical School, Brigham and Women s Hospital, Boston, MA 02115, USA
J Cell Biol 169:871-84. 2005..We propose that mRNA released from disassembled polysomes is sorted and remodeled at SGs, from which selected transcripts are delivered to PBs for degradation...
- Cytoprotection by pre-emptive conditional phosphorylation of translation initiation factor 2Phoebe D Lu
Skirball Institute, New York University School of Medicine, New York, NY, USA
EMBO J 23:169-79. 2004....
- Translational repression mediates activation of nuclear factor kappa B by phosphorylated translation initiation factor 2Jing Deng
New York University Medical Center, SI 3 10, 540 First Ave, New York, NY 10016, USA
Mol Cell Biol 24:10161-8. 2004..These studies suggest a direct role for eIF2alpha phosphorylation-dependent translational control in activating NF-kappaB during ER stress...
- The zipper model of translational control: a small upstream ORF is the switch that controls structural remodeling of an mRNA leaderIbrahim Yaman
Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
Cell 113:519-31. 2003..This study suggests that the structure of the IRES is dynamic and regulation of this RNA structure is a mechanism of translational control...
- Heme-regulated inhibitor kinase-mediated phosphorylation of eukaryotic translation initiation factor 2 inhibits translation, induces stress granule formation, and mediates survival upon arsenite exposureEdward McEwen
Howard Hughes Medical Institute and the Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor 48109, USA
J Biol Chem 280:16925-33. 2005..The results demonstrated an essential role for HRI in mediating arsenite stress-induced phosphorylation of eukaryotic translation initiation factor 2alpha, inhibition of protein synthesis, stress granule formation, and survival...