Research Topics
Genomes and Genes
| D RonSummaryAffiliation: New York University Country: USA Publications
| Collaborators
|
Detail Information
Publications
Cell biology. Stressed cells cope with protein overloadDavid Ron
Skirball Institute, New York University Medical Center, 540 First Avenue, New York, NY 10016, USA
Science 313:52-3. 2006
Regulated association of misfolded endoplasmic reticulum lumenal proteins with P58/DNAJc3Kseniya Petrova
Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
EMBO J 27:2862-72. 2008..These findings are consistent with a model whereby localized activation of the Hsp70-type partner is sufficient to promote substrate handover from the J-domain co-chaperone...
How IRE1 reacts to ER stressDavid Ron
Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
Cell 132:24-6. 2008..2008). This structure provides new insight into the mysterious coupling of kinase and endoribonuclease activities in the oldest, most-conserved branch of the unfolded protein response in eukaryotes...
Membrane biogenesis and the unfolded protein responseDavid Ron
Skirball Institute of Biomolecular Medicine, School of Medicine, New York University, New York, NY 10016, USA
J Cell Biol 167:23-5. 2004..The new data lend direct support for this idea and imply interesting mechanistic possibilities for how this coupling develops...
Signal integration in the endoplasmic reticulum unfolded protein responseDavid Ron
The Kimmel Center for Biology and Medicine at the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA
Nat Rev Mol Cell Biol 8:519-29. 2007..The arms of the UPR are integrated to provide a response that remodels the secretory apparatus and aligns cellular physiology to the demands imposed by ER stress...
Translational control in the endoplasmic reticulum stress responseDavid Ron
Skirball Institute of Biomolecular Medicine, Department of Medicine, New York, New York 10016, USA
J Clin Invest 110:1383-8. 2002
Targeting translation in hypoxic tumorsDavid Ron
Skirball Institute of Biomolecular Medicine and the Department of Medicine, New York University School of Medicine, New York, New York 10016, USA
ACS Chem Biol 1:145-8. 2006....
Proteotoxicity in the endoplasmic reticulum: lessons from the Akita diabetic mouseDavid Ron
Skirball Institute of Biomolecular Medicine, Department of Medicine, New York University School of Medicine, New York, New York 10016, USA
J Clin Invest 109:443-5. 2002
Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alphaI Novoa
Skirball Institute of Biomolecular Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA
J Cell Biol 153:1011-22. 2001....
Regulated translation initiation controls stress-induced gene expression in mammalian cellsH P Harding
Skirball Institute of Biomolecular Medicine The Department of Medicine, Kaplan Cancer Center New York University School of Medicine, New York, NY 10016, USA
Mol Cell 6:1099-108. 2000..Mammalian cells thus utilize an ancient pathway to regulate gene expression in response to diverse stress signals...
Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinaseH P Harding
Skirball Institute of Biomolecular Medicine, Department of Medicine, NYU School of Medicine, New York 10016, USA
Nature 397:271-4. 1999..These properties implicate PERK in a signalling pathway that attenuates protein translation in response to ER stress...
Identification of novel stress-induced genes downstream of chopX Z Wang
Skirball Institute of Biomolecular Medicine, the Departments of Medicine, Cell Biology and the Kaplan Cancer Center, NYU Medical Center, New York, NY 10016, USA
EMBO J 17:3619-30. 1998..These results reveal the existence of a novel CHOP-dependent signaling pathway, distinct from the known endoplasmic reticulum unfolded protein response, which may mediate changes in cell phenotype in response to stress...
Cloning of mammalian Ire1 reveals diversity in the ER stress responsesX Z Wang
Skirball Institute of Biomolecular Medicine, the Departments of Medicine, Cell Biology and the Kaplan Cancer Center, NYU Medical Center, New York, NY 10016, USA
EMBO J 17:5708-17. 1998..These results indicate that a single upstream component, Ire1, plays a role in multiple facets of the ER stress-response in mammalian cells...
Diabetes mellitus and exocrine pancreatic dysfunction in perk-/- mice reveals a role for translational control in secretory cell survivalH P Harding
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 10016, New York, NY, USA
Mol Cell 7:1153-63. 2001..These findings suggest a special role for translational control in protecting secretory cells from ER stress...
Dynamic interaction of BiP and ER stress transducers in the unfolded-protein responseA Bertolotti
Skirball Institute of Biomolecular Medicine, Departments of Medicine and Cell Biology and the Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA
Nat Cell Biol 2:326-32. 2000..These findings are consistent with a model in which BiP represses signalling through PERK and IRE1 and protein misfolding relieves this repression by effecting the release of BiP from the PERK and IRE1 lumenal domains...
Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1F Urano
Skirball Institute of Biomolecular Medicine, Departments of Medicine, Cell Biology and the Kaplan Cancer Center, New York University Medical School, New York, NY 10016, USA
Science 287:664-6. 2000..Dominant-negative TRAF2 inhibited activation of JNK by IRE1. Activation of JNK by endogenous signals initiated in the ER proceeds by a pathway similar to that initiated by cell surface receptors in response to extracellular signals...
Male sterility and enhanced radiation sensitivity in TLS(-/-) miceM Kuroda
Skirball Institute of Biomolecular Medicine, the Departments of Medicine, Cell Biology and the Kaplan Cancer Center, NYU Medical Center, New York, NY 10016, USA
EMBO J 19:453-62. 2000..These results are consistent with a role for TLS in homologous DNA pairing and recombination...
A topogenic role for the oncogenic N-terminus of TLS: nucleolar localization when transcription is inhibitedH Zinszner
Department of Medicine, Skirball Institute of Biomolecular Medicine, NYU Medical Center, New York, NY 10016, USA
Oncogene 14:451-61. 1997....
Perk is essential for translational regulation and cell survival during the unfolded protein responseH P Harding
Department of Medicine, The Kaplan Cancer Center, New York University School of Medicine, New York 10016, USA
Mol Cell 5:897-904. 2000..PERK thus plays a major role in the ability of cells to adapt to ER stress...
Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcomaA Crozat
Department of Medicine, NYU Medical Center, New York 10016
Nature 363:640-4. 1993..In TLS-CHOP the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. Targeting of a conserved effector domain of RNA-binding proteins to DNA may play a role in tumour formation...
TLS (FUS) binds RNA in vivo and engages in nucleo-cytoplasmic shuttlingH Zinszner
Skirball Institute of Biomolecular Medicine, the Deparment of Medicine, NYU Medical Center, New York 10016, USA
J Cell Sci 110:1741-50. 1997..These findings are discussed in the context of the role altered forms of TLS play in cellular transformation...
CHOP-Dependent stress-inducible expression of a novel form of carbonic anhydrase VIJ Sok
Skirball Institute of Biomolecular Medicine, Departments of Medicine and Cell Biology, and Kaplan Cancer Center, New York University Medical Center, New York, New York 10016, USA
Mol Cell Biol 19:495-504. 1999....
Induction of a secreted protein by the myxoid liposarcoma oncogeneM Kuroda
Skirball Institute of Biomolecular Medicine, Departments of Medicine, Cell Biology, and the Kaplan Cancer Center, New York University Medical Center, New York, NY 10016, USA
Proc Natl Acad Sci U S A 96:5025-30. 1999..TLS-CHOP thus leads to the unscheduled expression of a gene that is normally associated with adipocytic differentiation...
Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153)X Z Wang
Department of Medicine, NYU Medical Center, New York 10016, USA
Mol Cell Biol 16:4273-80. 1996..These results suggest that CHOP is more responsive to ER stress than to growth arrest or DNA damage and indicate a potential role for CHOP in linking stress in the ER to alterations in gene expression...
Increased sensitivity to dextran sodium sulfate colitis in IRE1beta-deficient miceA Bertolotti
Skirball Institute of Biomolecular Medicine, Departments of Medicine and Cell Biology, and the Kaplan Cancer Center, New York University School of Medicine, New York, New York, USA
J Clin Invest 107:585-93. 2001..These findings are consistent with a model whereby perturbations in ER function, which are normally mitigated by the activity of IRE1beta, participate in the development of colitis...
Inhibition of adipogenesis by the stress-induced protein CHOP (Gadd153)N Batchvarova
Skirball Institute of Biomolecular Medicine, Department of Medicine, New York University Medical Center, NY 10016, USA
EMBO J 14:4654-61. 1995..Our data suggest that CHOP functions as an inducible inhibitor of adipocytic differentiation in response to metabolic stress. It does so by interfering with the accumulation of adipogenic C/EBP isoforms...
Alterations in an IRE1-RNA complex in the mammalian unfolded protein responseA Bertolotti
Skirball Institute of Biomolecular Medicine, and the Kaplan Cancer Center, New York University School of Medicine, New York, NY 10016, USA
J Cell Sci 114:3207-12. 2001..When viewed in the context of the known importance of Ire1p-HAC1 mRNA interactions to the yeast unfolded protein response, these findings suggest that full-length mammalian IRE1s also engage RNA molecules as downstream effectors...
Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPKWei Yan
Departments of Microbiology and Laboratory Medicine, School of Medicine, and Washington National Primate Research Center, University of Washington, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 99:15920-5. 2002..Our studies suggest that P58(IPK) induction during the ER-stress response represses PERK activity and plays a functional role in the expression of downstream markers of PERK activity in the later phase of the ER-stress response...
gamma-heregulin is the product of a chromosomal translocation fusing the DOC4 and HGL/NRG1 genes in the MDA-MB-175 breast cancer cell lineX Z Wang
Department of Medicine, Skirball Institute of Biomolecular Medicine, Kaplan Cancer Center, NYU Medical Center, New York, NY 10016, USA
Oncogene 18:5718-21. 1999..We speculate that the mutation may be selected for by virtue of its ability to activate ErbB signaling through the production of an autocrine ligand...
IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNAMarcella Calfon
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
Nature 415:92-6. 2002..Our findings suggest that physiological ER load regulates a developmental decision in higher eukaryotes...
Stress-induced gene expression requires programmed recovery from translational repressionIsabel Novoa
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
EMBO J 22:1180-7. 2003....
ERO1-beta, a pancreas-specific disulfide oxidase, promotes insulin biogenesis and glucose homeostasisEster Zito
Helen L and Martin S Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
J Cell Biol 188:821-32. 2010..These findings point to an unexpectedly selective function for ERO1-beta in oxidative protein folding in insulin-producing cells that is required for glucose homeostasis in vivo...
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....
Arsenite-inducible RNA-associated protein (AIRAP) protects cells from arsenite toxicityJ Sok
Department of Medicine, Skirball Institute of Biomolecular Medicine, and the Kaplan Cancer Center, New York University School of Medicine, NY 10016, USA
Cell Stress Chaperones 6:6-15. 2001..These experiments suggest a role for AIRAP/AIP-1 in protecting cells from the toxic effects of arsenite...
CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulumH Zinszner
Skirball Institute of Biomolecular Medicine, the Departments of Medicine, Cell Biology, and the Kaplan Cancer Center, New York University NYU Medical Center, New York, New York 10016 USA
Genes Dev 12:982-95. 1998..CHOP therefore has a role in the induction of cell death under conditions associated with malfunction of the ER and may also have a role in cellular regeneration under such circumstances...
Cotranslocational degradation protects the stressed endoplasmic reticulum from protein overloadSeiichi Oyadomari
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
Cell 126:727-39. 2006..Thus, P58(IPK) is a key mediator of cotranslocational ER protein degradation, and this process likely contributes to ER homeostasis in stressed cells...
CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulumStefan J Marciniak
Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA
Genes Dev 18:3066-77. 2004..CHOP deletion thus protects cells from ER stress by decreasing ER client protein load and changing redox conditions within the organelle...
Targeting of mRNAs to their sites of unconventional splicing in the unfolded protein responseDavid Ron
Skirball Institute, NYU School of Medicine, New York, NY 10016, USA
Mol Cell 34:133-4. 2009..2009) are reports on the importance of mRNA localization for unconventional splicing in the unfolded protein response, but the two papers suggest very different mechanisms in mammals and yeast...
Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP KinaseX Z Wang
Department of Medicine, Skirball Institute of Biomolecular Medicine, New York University Medical Center, 10016, NY, USA
Science 272:1347-9. 1996..CHOP thus serves as a link between a specific stress-activated protein kinase, p38, and cellular growth and differentiation...
Endoplasmic reticulum stress and the unfolded protein response in cellular models of Parkinson's diseaseElizabeth J Ryu
Department of Pathology, Center for Neurobiology and Behavior, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
J Neurosci 22:10690-8. 2002..Our findings, coupled with evidence from familial forms of Parkinson's disease, raise the possibility of widespread involvement of endoplasmic reticulum stress and the unfolded protein response in the pathophysiology of this disease...
Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperonesTakunari Yoneda
Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
J Cell Sci 117:4055-66. 2004..These observations support the existence of a mitochondrial unfolded protein response that couples mitochondrial chaperone gene expression to changes in the protein handling environment in the organelle...
The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophagesBo Feng
Department of Medicine, Columbia University, New York, NY 10032, USA
Nat Cell Biol 5:781-92. 2003..We propose that cholesterol trafficking to endoplasmic reticulum membranes, resulting in activation of the CHOP arm of the UPR, is the key signalling step in cholesterol-induced apoptosis in macrophages...
Flavonol activation defines an unanticipated ligand-binding site in the kinase-RNase domain of IRE1R Luke Wiseman
Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
Mol Cell 38:291-304. 2010....
A survival pathway for Caenorhabditis elegans with a blocked unfolded protein responseFumihiko Urano
Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
J Cell Biol 158:639-46. 2002....
Association of SARFH (sarcoma-associated RNA-binding fly homolog) with regions of chromatin transcribed by RNA polymerase IID Immanuel
Skirball Institute of Biomolecular Medicine, Department of Medicine, New York University Medical Center, New York 10016, USA
Mol Cell Biol 15:4562-71. 1995..We conclude that SARFH and, by homology, EWS and TLS participate in a function common to the expression of most genes transcribed by RNA Pol II...
Characterization of phosphopeptides from protein digests using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and nanoelectrospray quadrupole time-of-flight mass spectrometryY Ma
Department of Pharmacology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
Rapid Commun Mass Spectrom 15:1693-700. 2001....
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...
A small molecule inhibitor of endoplasmic reticulum oxidation 1 (ERO1) with selectively reversible thiol reactivityJaime D Blais
Kimmel Center for Biology and Medicine of the Skirball Institute and the Departments of Cell Biology and Medicine, New York University School of Medicine, New York, NY 10016, USA
J Biol Chem 285:20993-1003. 2010..Together, these observations point to the feasibility of targeting the enzymatic activity of ERO1alpha with small molecule inhibitors...
An intact unfolded protein response in Trpt1 knockout mice reveals phylogenic divergence in pathways for RNA ligationHeather P Harding
Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA
RNA 14:225-32. 2008..These observations argue against the presence of a 2'-PO4(2-) at the splice junction of ligated RNA molecules in Trpt1-/- cells, and suggest that Xbp-1 and tRNA ligation proceed by distinct pathways in yeast and mammals...
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...
Lipid phase perturbations and the unfolded protein responseDavid Ron
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
Dev Cell 7:287-8. 2004....
Transcriptional and translational control in the Mammalian unfolded protein responseHeather P Harding
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York 10016, USA
Annu Rev Cell Dev Biol 18:575-99. 2002..Together, these two components adapt the secretory apparatus to physiological load and protect cells from the consequences of protein malfolding...
An integrated stress response regulates amino acid metabolism and resistance to oxidative stressHeather P Harding
Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
Mol Cell 11:619-33. 2003..A signaling pathway initiated by eIF2alpha phosphorylation protects cells against metabolic consequences of ER oxidation by promoting the linked processes of amino acid sufficiency and resistance to oxidative stress...
Endoplasmic reticulum stress and the development of diabetes: a reviewHeather P Harding
Skirball Institute, New York University School of Medicine, New York, New York 10016, USA
Diabetes 51:S455-61. 2002..We will review this and other rare forms of clinical and experimental diabetes and consider the role of ER stress in the development of more common forms of the disease...
Translation reinitiation at alternative open reading frames regulates gene expression in an integrated stress responsePhoebe D Lu
Department of Cell Biology, School of Medicine, New York University, New York, NY 10016, USA
J Cell Biol 167:27-33. 2004..These features are common to regulated translation of GCN4 in yeast. The metazoan ISR thus resembles the yeast general control response both in its target genes and its mechanistic details...
Inhibition of a constitutive translation initiation factor 2alpha phosphatase, CReP, promotes survival of stressed cellsCéline Jousse
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
J Cell Biol 163:767-75. 2003..These findings suggest that therapeutic inhibition of eIF2alpha dephosphorylation by targeting the CReP-protein-phosphatase-1 complex may be used to access the salubrious qualities of the ISR...
Activation-dependent substrate recruitment by the eukaryotic translation initiation factor 2 kinase PERKStefan J Marciniak
Skirball Institute of Biomolecular Medicine, New York, NY 10016, USA
J Cell Biol 172:201-9. 2006..Our findings suggest a novel mechanism for eIF2 recruitment by activated PERK and for unidirectional substrate flow in the phosphorylation reaction...
Ubiquitin-like protein 5 positively regulates chaperone gene expression in the mitochondrial unfolded protein responseCristina Benedetti
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
Genetics 174:229-39. 2006..Induction of mitochondrial stress promotes accumulation of GFP-tagged UBL-5 in nuclei of transgenic worms, suggesting that UBL-5 effects a nuclear step required for mounting a response to the threat of mitochondrial protein misfolding...
Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosisGang Li
Department of Medicine, Columbia University, New York, NY 10032, USA
J Cell Biol 186:783-92. 2009..Macrophages from insulin-resistant ob/ob mice, another model of ER stress, also have elevated IICR. These data shed new light on how the CHOP pathway of apoptosis triggers calcium-dependent apoptosis through an ERO1-alpha-IP3R pathway...
ClpP mediates activation of a mitochondrial unfolded protein response in C. elegansCole M Haynes
Kimmel Center for Biology and Medicine of Skirball Institute and Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA
Dev Cell 13:467-80. 2007..As ClpP is known to function in the bacterial heat-shock response, our findings suggest that eukaryotes utilize component(s) from the protomitochondrial symbiont to signal the UPR(mt)...
Thioredoxin-related Protein 32 is an arsenite-regulated Thiol Reductase of the proteasome 19 S particleR Luke Wiseman
Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA
J Biol Chem 284:15233-45. 2009..These findings reveal a previously undescribed thiol reductase at the proteasome's regulatory particle...
Reduced apoptosis and plaque necrosis in advanced atherosclerotic lesions of Apoe-/- and Ldlr-/- mice lacking CHOPEdward Thorp
Department of Medicine, Columbia University, New York, NY 10032, USA
Cell Metab 9:474-81. 2009..These data provide direct evidence for a causal link between the ER stress effector CHOP and plaque necrosis and suggest that interventions weakening this arm of the UPR may lessen plaque progression...
Transmission of proteotoxicity across cellular compartmentsTakunari Yoneda
Skirball Institute of Biomolecular Medicine, Department of Medicine, New York University School of Medicine, New York 10016, USA
Genes Dev 16:1307-13. 2002
Adaptive suppression of the ATF4-CHOP branch of the unfolded protein response by toll-like receptor signallingConnie W Woo
Department of Medicine, Columbia University, New York, NY 10032, USA
Nat Cell Biol 11:1473-80. 2009..We speculate that this mechanism evolved to promote survival of TLR-expressing cells that experience prolonged levels of physiological ER stress in the course of the host response to invading pathogens...
The matrix peptide exporter HAF-1 signals a mitochondrial UPR by activating the transcription factor ZC376.7 in C. elegansCole M Haynes
Kimmel Center for Biology and Medicine of the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
Mol Cell 37:529-40. 2010....
An arsenite-inducible 19S regulatory particle-associated protein adapts proteasomes to proteotoxicityAriel Stanhill
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
Mol Cell 23:875-85. 2006..These features include enhanced cleavage of peptide substrates and suggest that AIRAP adapts the cell's core protein degradation machinery to counteract proteotoxicity induced by an environmental toxin...
Heat shock protein 90 modulates the unfolded protein response by stabilizing IRE1alphaMonica G Marcu
Cell and Cancer Biology Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850, USA
Mol Cell Biol 22:8506-13. 2002..These data establish a role for HSP90 in the cellular transcriptional response to ER stress and demonstrate that chaperone systems on both sides of the ER membrane serve to integrate this signal transduction cascade...
Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viabilityWen Xing Ding
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15231, USA
Am J Pathol 171:513-24. 2007..Our studies thus provide a mechanistic view and elucidate the functional significance of the link between the two protein degradation systems...
Mammalian stress granules represent sites of accumulation of stalled translation initiation complexesScot R Kimball
Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
Am J Physiol Cell Physiol 284:C273-84. 2003..Finally, we also show that stress granules contain many, if not all, of the components of the 48S preinitiation complex, but not 60S ribosomal subunits, suggesting that they represent stalled translation initiation complexes...
IRE1beta inhibits chylomicron production by selectively degrading MTP mRNAJahangir Iqbal
Department of Anatomy and Cell Biology and Department of Pediatrics, The State University of New York Downstate Medical Center, Brooklyn, NY 11203, USA
Cell Metab 7:445-55. 2008..Conversely, knockdown of IRE1beta enhanced MTP expression. These studies show that IRE1beta plays a role in regulating MTP and in chylomicron production...
Novel function of PERK as a mediator of force-induced apoptosisBaldwin C Mak
Canadian Institutes of Health Research Group in Matrix Dynamics, University of Toronto, Toronto, Ontario M5S 3E2, Canada
J Biol Chem 283:23462-72. 2008..We conclude that force-induced apoptosis depends on a novel function of PERK that occurs in addition to its canonical role in the unfolded protein response...
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...
Endoplasmic reticulum stress modulates the response of myelinating oligodendrocytes to the immune cytokine interferon-gammaWensheng Lin
Jack Miller Center for Peripheral Neuropathy, Department of Neurology, University of Chicago, Chicago, IL 60637, USA
J Cell Biol 169:603-12. 2005..Therefore, the hypersensitivity of PERK+/- mice to IFN-gamma implicates ER stress in demyelinating disorders that are induced by CNS inflammation...
Transmission of cell stress from endoplasmic reticulum to mitochondria: enhanced expression of Lon proteaseOsamu Hori
Department of Neuroanatomy, Kanazawa University, School of Medicine, Kanazawa City, Ishikawa 920 8640, Japan
J Cell Biol 157:1151-60. 2002....
Proteasomal adaptation to environmental stress links resistance to proteotoxicity with longevity in Caenorhabditis elegansChi Yun
The Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine
Proc Natl Acad Sci U S A 105:7094-9. 2008..In worms, a single AIRAP-related protein links proteasomal adaptation to environmental stress with resistance to both proteotoxic insults and maintenance of animal life span under normal conditions...
Translation attenuation by PERK balances ER glycoprotein synthesis with lipid-linked oligosaccharide fluxJie Shang
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
J Cell Biol 176:605-16. 2007..Thus, by sensing ER stress from defective glycosylation, PERK can restore ER homeostasis by balancing polypeptide synthesis with flux through the LLO pathway...
The integrated stress response prevents demyelination by protecting oligodendrocytes against immune-mediated damageWensheng Lin
Jack Miller Center for Peripheral Neuropathy, Department of Neurology, The University of Chicago, Chicago, Illinois 60637, USA
J Clin Invest 117:448-56. 2007..Our results indicate that IFN-gamma activation of PERK in mature oligodendrocytes attenuates EAE severity and suggest that therapeutic approaches to activate the ISR could prove beneficial in MS...
A membrane protein complex mediates retro-translocation from the ER lumen into the cytosolYihong Ye
Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
Nature 429:841-7. 2004..Derlin-1 interacts with US11, a virally encoded ER protein that specifically targets MHC class I heavy chains for export from the ER, as well as with VIMP, a novel membrane protein that recruits the p97 ATPase and its cofactor...
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...
GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenaseDavid H Munn
Department of Pediatrics, Medical College of Georgia, Augusta, GA 30912, USA
Immunity 22:633-42. 2005..We hypothesize that GCN2 acts as a molecular sensor in T cells, allowing them to detect and respond to conditions created by IDO...
The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivoresAnne Catherine Maurin
Unité de Nutrition et Métabolisme Protéique, Institut National de la Recherche Agronomique de Theix, 63122 Saint Genes Champanelle, France
Cell Metab 1:273-7. 2005..An ancient intracellular signal transduction pathway responsive to amino acid deficiency thus affects feeding behavior by activating a neuronal circuit that biases consumption against imbalanced food sources...
CHOP/GADD153 is a mediator of apoptotic death in substantia nigra dopamine neurons in an in vivo neurotoxin model of parkinsonismRobert M Silva
Department of Neurology, The College of Physicians and Surgeons, Columbia University, New York 10032, USA
J Neurochem 95:974-86. 2005..We conclude that the role of CHOP depends on the nature of the toxic stimulus. For 6OHDA, an oxidative metabolite of dopamine, it is a mediator of apoptotic death...
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...
Rapid B cell receptor-induced unfolded protein response in nonsecretory B cells correlates with pro- versus antiapoptotic cell fateAlison H Skalet
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 280:39762-71. 2005..These studies establish a system whereby a terminal or adaptive UPR can be alternatively triggered by physiologic stimuli...
Activating transcription factor 4 is translationally regulated by hypoxic stressJaime D Blais
Ottawa Regional Cancer Center, Ontario, Canada
Mol Cell Biol 24:7469-82. 2004..Taken with the concomitant induction of additional ER-resident proteins identified by our microarray analysis, this study suggests an important integrated response between ER signaling and the cellular adaptation to hypoxic stress...
Role for activating transcription factor 3 in stress-induced beta-cell apoptosisMatthew G Hartman
Department of Molecular and Cellular Biochemistry, Center for Molecular Neurobiology, Ohio State University, Columbus, USA
Mol Cell Biol 24:5721-32. 2004..Taken together, our results suggest ATF3 to be a novel regulator of stress-induced beta-cell apoptosis...
ER stress disrupts Ca2+-signaling complexes and Ca2+ regulation in secretory and muscle cells from PERK-knockout miceGuojin Huang
Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
J Cell Sci 119:153-61. 2006....
Modulation of the eukaryotic initiation factor 2 alpha-subunit kinase PERK by tyrosine phosphorylationQiaozhu Su
Lady Davis Institute for Medical Research, McGiIl University, Sir Mortimer B Davis Jewish General Hospital, 3999 Côte Ste Catherine Street, Montreal, Quebec, Canada
J Biol Chem 283:469-75. 2008..Thus, our data classify PERK as a dual specificity kinase whose regulation by tyrosine phosphorylation contributes to its optimal activation in response to ER stress...
Activating transcription factor 3 is integral to the eukaryotic initiation factor 2 kinase stress responseHao Yuan Jiang
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
Mol Cell Biol 24:1365-77. 2004....
C/EBP homologous protein is necessary for normal osteoblastic functionRenata C Pereira
Department of Research, Saint Francis Hospital and Medical Center, 114 Woodland Street, Hartford, CT 06105 1299, USA
J Cell Biochem 97:633-40. 2006..In conclusion, chop null mice exhibit decreased bone formation and impaired osteoblastic function, indicating that CHOP is necessary for the normal expression of the osteoblastic phenotype...
Oligodendrocytes are a major target of the toxicity of spongiogenic murine retrovirusesAmanda C Clase
Laboratory of Persistent Viral Diseases, The Microscopy Unit, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 S 4th St, Hamilton, MT 59840, USA
Am J Pathol 169:1026-38. 2006..This observation may link the cellular pathology observed in the brain with cellular stress responses known to be induced by these viruses. The relevance of these observations to oligodendropathy in humans is discussed...
Translocated in liposarcoma (TLS) is a substrate for fibroblast growth factor receptor-1Peter Klint
Rudbeck Laboratory, Department of Genetics and Pathology, 751 85, Uppsala, Sweden
Cell Signal 16:515-20. 2004..We show that TLS is tyrosine phosphorylated in intact cells by a number of different growth factors, indicating a role in growth regulation...
The dynamic ER: experimental approaches and current questionsChristine M Federovitch
UCSD Division of Biological Sciences, Section of Cell and Developmental Biology, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Curr Opin Cell Biol 17:409-14. 2005..Because of the ER's key functions in protein and lipid synthesis, this organelle is a hotbed of detailed molecular analysis...
Antiviral effect of the mammalian translation initiation factor 2alpha kinase GCN2 against RNA virusesJuan J Berlanga
Centro de Biologia Molecular Severo Ochoa, CSIC UAM, Facultad de Ciencias, Cantoblanco, Universidad Autonoma de Madrid, Madrid, Spain
EMBO J 25:1730-40. 2006..We determined that GCN2 inhibits SV replication by blocking early viral translation of genomic SV RNA. These findings point to a hitherto unrecognized role of GCN2 as an early mediator in the cellular response to RNA viruses...
Translational control of hippocampal synaptic plasticity and memory by the eIF2alpha kinase GCN2Mauro Costa-Mattioli
Department of Biochemistry and McGill Cancer Center, Montreal, Quebec, Canada
Nature 436:1166-73. 2005..Our study provides genetic, physiological, behavioural and molecular evidence that GCN2 regulates synaptic plasticity, as well as learning and memory, through modulation of the ATF4/CREB pathway...
Interferon-gamma inhibits central nervous system remyelination through a process modulated by endoplasmic reticulum stressWensheng Lin
Department of Neurology, Jack Miller Center for Peripheral Neuropathy, University of Chicago, Chicago, IL 60637, USA
Brain 129:1306-18. 2006..Thus, these data suggest that IFN-gamma is capable of inhibiting remyelination in demyelinated lesions and that ER stress modulates the response of remyelinating oligodendrocytes to this cytokine...
Ablation of the UPR-mediator CHOP restores motor function and reduces demyelination in Charcot-Marie-Tooth 1B miceMaria Pennuto
DIBIT, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy
Neuron 57:393-405. 2008..S63del mice also provide an opportunity to explore how cells can dysfunction yet survive in prolonged ER stress-important for neurodegeneration related to misfolded proteins...
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...
