Ron Lab


Selected Original Reports:

    Crespillo-Casado A, Claes Z, Choy MS, Peti W, Bollen M and Ron D. 2018. A sephin1-insensitive tripartite holophosphatase dephosphorylates translation initiation factor 2alpha. J. Biol. Chem. (10.1074/jbc.RA118.002325) (PMID: 29618508)

    Zyryanova AF, Weis F, Faille A, Alard AA, Crespillo-Casado A, Sekine Y, Harding HP, Allen F, Parts L, Fromont C, Fischer PM, Warren AJ and Ron D. 2018. Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B. Science 359:1533-6 (PMID: 29599245)

    Amin-Wetzel N, Saunders RA, Kamphuis MJ, Rato C, Preissler S, Harding HP and Ron D. 2017. A J-protein co-chaperone recruits BiP to monomerize IRE1 and repress the unfolded protein response. Cell 171:1625-37 (10.1016/j.cell.2017.10.040) (PMID: 29198525)

    Preissler S, Rohland L, Yan Y, Chen R, Read RJ and Ron D. 2017. AMPylation targets the rate-limiting step of BiP’s ATPase cycle for its functional inactivation. Elife 6:e29428 (PMID: 29064368)

    Kono N, Amin-Wetzel N and Ron D. 2017. Generic membrane spanning features endow IRE1a with responsiveness to membrane aberrancy. Mol. Biol. Cell 28:2318-32 (10.1091/mbc.E17-03-0144) (PMID: 28615323)

    Crespillo-Casado A, Chambers JE, Fischer PM, Marciniak SJ and Ron D. 2017. Ppp1r15a-mediated dephosphorylation of eif2a is unaffected by sephin1 or guanabenz. Elife 6:e26109 (PMID: 28447936)

    Melo EP, Lopes C, Gollwitzer P, Lortz S, Lenzen S, Mehmeti I, Kaminski CF, Ron D and Avezov E. 2017. Triper, an optical probe tuned to the endoplasmic reticulum tracks changes in luminal H2O2. BMC Biol. 15:24 (10.1186/s12915-017-0367-5) (PMID: 28347335)

    Preissler S, Rato C, Perera LA, Saudek V and Ron D. 2017. FICD acts bifunctionally to AMPylate and de-AMPylate the endoplasmic reticulum chaperone BiP. Nat. Struct. Mol. Biol. 24:23-9 (10.1038/nsmb.3337) (PMID: 27918543)

    Preissler S, Rato C, Chen R, Antrobus R, Ding S, Fearnley IM and Ron D. 2015. AMPylation matches BiP activity to client protein load in the endoplasmic reticulum. eLIFE 4:(10.7554/eLife.12621) (PMID: 26673894)

    Konno T, Pinho Melo E, Lopes C, Mehmeti I, Lenzen S, Ron D and Avezov E. 2015. Ero1-independent production of H2O2 within the endoplasmic reticulum fuels PRDX4-mediated oxidative protein folding. J. Cell Biol. 211:253-9 (10.1083/jcb.201506123) (PMID: 26504166)

    Preissler S, Chambers JE, Crespillo-Casado A, Avezov E, Miranda E, Perez J, Hendershot LM, Harding HP and Ron D. 2015. Physiological modulation of BiP activity by trans-protomer engagement of the interdomain linker. eLIFE 4:(10.7554/eLife.08961) (PMID: 26473973)

    Sekine Y, Zyryanova A, Crespillo-Casado A, Fischer PM, Harding HP and Ron D. 2015. Mutations in a translation initiation factor identify the target of a memory-enhancing compound. Science 348:1027-1030(10.1126/science.aaa6986) (PMID: 25858979). See perspective article by Alan Hinnebusch.

    Chen R, Rato C, Yan Y, Crespillo-Casado A, Clarke HJ, Harding HP, Marciniak SJ, Read RJ and Ron D. 2015. G-actin provides substrate-specificity to eukaryotic initiation factor 2a holophosphatase. eLIFE 4:(10.7554/eLife.04871) (PMID: 25774600)

    Chambers JE, Dalton LE, Clarke HJ, Malzer E, Dominicus CS, Patel V, Moorhead G, Ron D and Marciniak SJ. 2015. Actin dynamics tune the integrated stress response by regulatins eukaryotic initiation factor 2α dephosphorylation. eLIFE 4:(10.7554/eLife.04872) (PMID: 25774599)

    Avezov E, Konno T, Zyryanova A, Chen W, Laine R, Crespillo-Casado A, Pinho Melo E, Ushioda R, Nagata K, Kaminski C, Harding HP and Ron D. 2015. Retarded PDI diffusion and a reductive shift in poise of the calcium depleted endoplasmic reticulum. BMC Biology DOI:10.1186/s12915-014-0112-2 (PMID: 25575667)

    Tsunoda S, Avezov E, Zyryanova A, Konno T, Mendes-Silva L, Pinho Melo E, Harding HP, and Ron D. 2014. Intact protein folding in the glutathione-depleted endoplasmic reticulum implicates alternative protein thiol reductants. eLIFE DOI: 10.7554/eLife.03421 (PMID: 25073928)

    Avezov E, Cross BC, Kaminski Schierle GS, Winters M, Harding HP, Melo EP, Kaminski CF and Ron D. 2013. Lifetime imaging of a fluorescent protein sensor reveals surprising stability of er thiol redox. J. Cell Biol. 201:337-49 (PMID: 23589496)

    Volmer R, van der Ploeg K and Ron D. 2013. Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains. Proc. Natl. Acad. Sci. U. S. A. 2013 110:4628-33. doi: 10.1073/pnas.1217611110. Epub 2013 Mar 4 (PMID: 23487760).

    Harding HP, Zyryanova AF and Ron D. 2012. Uncoupling proteostasis and development in vitro with a small molecule inhibitor of the pancreatic endoplasmic reticulum kinase, PERK. J. Biol. Chem. 287:44338-44 (PMID: 23148209) (access to online version on publisher's website). Note: the compound described in the paper is now available commercially from Millipore Calbiochem (Cat. 516535).

    Zito E, Hansen H, Yeo G, Fujii J and Ron D. 2012. Endoplasmic reticulum thiol oxidase deficiency leads to ascorbic acid depletion and non-canonical scurvy in mice. Mol. Cell 48:39-51 (PMID: 22981861) (access to final version on publisher's website)

    Chambers JE, Petrova K, Tomba G, Vendruscolo M and Ron D. 2012. ADP ribosylation adapts an ER chaperone response to short-term fluctuations in unfolded protein load. J. Cell Biol. 198:371-85 (PMID: 22869598). Also see commentary by Pincus and Walter in: J. Cell Biol. 198:277-9 (PMID: 22869593).

    Cross BCS, Bond PJ, Sadowski PG, Jha BK, Zak J, Goodman JM, Silverman RH, Neubert TA, Baxendale IR, Ron D and Harding HP. 2012. The molecular basis for selective inhibition of unconventional mrna splicing by an IRE1-binding small molecule. Proc. Natl. Acad. Sci. U. S. A. 109:E869-E878 (PMID: 22315414). Note: 4µ8C, the IRE1 inhibitor discovered in our lab is commercially available from Tocris bioscience.

    Chin KT, Kang G, Qu J, Gardner LB, Coetzee WA, Zito E, Fishman GI and Ron D. 2011. The sarcoplasmic reticulum luminal thiol oxidase ero1 regulates cardiomyocyte excitation-coupled calcium release and response to hemodynamic load. FASEB J. 25:2583-2591 (PMID: 21507899)

    Tsaytler P, Harding HP, Ron D and Bertolotti A. 2011. Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis. Science 332:91-4 (PMID: 21385720). See commentary by Jeff Kelly and R. Luke Wiseman (PMID: 21454777)

    Zito E, Pinho Melo E, Yang Y, Wahlander Å, Neubert TA and Ron D. 2010. Oxidative protein folding by an endoplasmic reticulum localized peroxiredoxin. Mol. Cell 40:787-797 (PMID: 21145486). See commentary by Debbie Fass (PMID: 21145477)

    Blais JD, Chin KT, Zito E, Zhang Y, Heldman N, Harding HP, Fass D, Thorpe C and Ron D. 2010. A small molecule inhibitor of endoplasmic reticulum oxidation 1 (ero1) with selectively reversible thiol reactivity. J. Biol. Chem. 285:20993-21003 (PMID: 20442408)

    Wiseman RL, Zhang Y, Lee KPK, Harding HP, Haynes CM, Price J, Sicheri F and Ron D. 2010. Flavonol activation defines an unanticipated ligand binding site in the kinase-rnase domain of IRE11. Mol. Cell 38:291-304 (PMID: 20417606). See commentary by Kevan Shokat (PMID: 20417596)

    Zito E, Chin KT, Blais J, Harding HP and Ron D. 2010. Ero1β, a pancreas-specific disulfide oxidase promotes insulin biogenesis and glucose homeostasis. J. Cell Biol. 188:821-832 (PMID: 20308425). See commentary by Carolyn Sevier (PMID: 20308423).

    Haynes CM, Yang Y, Blais SP, Neubert TA and Ron D. 2010. The matrix peptide exporter haf-1 signals a mitochondrial unfolded protein response by activating the transcription factor zc376.7 in C. Elegans. Mol. Cell 37:529-40 (PMID: 20188671). See commentary by Janine Kirstein-Miles and Rick Morimoto

    Harding HP, Zhang Y, Scheuner D, Chen J-J, Kaufman RJ and Ron D. 2009. Ppp1r15 gene knockout reveals an essential role for translation initiation factor 2 alpha dephosphorylation in mammalian development. Proc Natl Acad Sci U S A 106:1832-1837 (PMID: 19181853). Download PDF

    Wiseman RL, Chin K-T, Haynes CM, Stanhill A, Xu C-F, Roguev A, Krogan NJ, Neubert TA and Ron D. 2009. Thioredoxin related protein 32 is an arsenite-regulated thiol reductase of the proteasome 19S particle. J Biol Chem 284:15233-45 (PMID: 19349280)

    Petrova K, Oyadomari S, Hendershot LM and Ron D. 2008. Regulated association of misfolded endoplasmic reticulum lumenal proteins with P58/DNAJc3. Embo J 27:2862-2872. Download PDF

    Oyadomari S, Harding HP, Zhang Y, Oyadomari M and Ron D.  2008.  De-phosphorylation of translation initiation factor 2α (eIF2α) enhances glucose tolerance and attenuates hepato-steatosis in mice. Cell Metab 7:520-532 Download pdf

    Yun C, Stanhill A, Yang Y, Zhang Y, Haynes CM, Xu C, Neubert T, Mor A, Philips MR and Ron D.  2008.  Proteasomal adaptation to environmental stress links resistance to proteotoxicity with longevity in C. elegans. Proc Natl Acad Sci U S A 105:7094-7099 Download pdf

    Harding HP, Lackey JG, Hsu HC, Zhang Y, Jing D, Xu RM, Damha MJ and Ron D.  2008.  An intact unfolded protein response in Trpt1 knockout mice reveals phylogenetic divergence in pathways for RNA ligation. RNA 14:225-232 Download pdf

    Haynes CM, Petrova K, Benedetti C, Yang Y and Ron D.  2007.  ClpP mediates activation of a mitochondrial unfolded protein response in C. elegans. Dev Cell. 13:467-480. Download pdf

    Stanhill A, Haynes CM, Zhang Y, Min G, Steele MC, Kalinina J, Martinez E, Pickart CM, Kong X.-P, and Ron D. 2006. An arsenite-inducible regulatory particle-associated protein (AIRAP) adapts proteasomes to proteotoxicity. Molecular Cell 23:875-885. Download pdf

    Benedetti C, Haynes CM, Yang Y, Harding HP and Ron D. 2006. Ubiquitin-like protein 5 positively regulates chaperone gene expression in the mitochondrial unfolded protein response. Genetics. 174:229-239. Download pdf

    Oyadomari S, Yun C, Fisher EA, Kreglinger N, Kreibich G, Oyadomari M, Harding HP, Goodman AG, Harrant H, Garrision JL, Taunton J, Katze MG and Ron D. 2006. Co-Translocational degradation protects the stressed endoplasmic reticulum from protein overload. Cell. 126:727-739. Download pdf. Also see commentary by Pearce & Hebert, correction of an error and unpublished NEW INFORMATION on P58IPK/DnajC3

    Marciniak SM, Garcia-Bonilla L, Hu J, Harding H and Ron D. 2006. Activation-dependent substrate recruitment by the eukaryotic translation initiation factor 2 kinase PERK. J Cell Biol 172:201-9. Download pdf

    Harding H, Zhang Y, Khershonsky S, Marciniak SM, Scheuner D, Kaufman RJ, Javitt N, Chang Y-T and Ron D. 2005. Bioactive small molecules reveal antagonism between the integrated stress response and sterol regulated gene expression. Cell Metabolism 2:361-71 (2005). Download pdf

    Maurin A, Jousse C, Averous J, Parry L, A B, Cherasse Y, Zeng H, Zhang Y, Harding H, Ron D and Fafournoux P. The GCN2 kinase biases feeding behavior to maintain amino-acid homeostasis in omnivores. Cell Metabolism. 1:273-277 (2005). Download pdf. Also see commentary by Dever and Hinnebusch.

    Marciniak SJ, Yun CY, Oyadomari S, Novoa I, Zhang Y, Jungreis R, Nagata K, Harding HP and Ron D. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes and Development. 18:3066-3077 (2004). Download pdf

    Deng J, Lu PD, Zhang Y, Scheuner D, Kaufman RJ, Sonenberg N, Harding HP and Ron D. Translational repression mediates activation of Nuclear Factor kappa B by phosphorylated translation initiation factor 2. Mol Cell Biol. 24:10161-10168 (2004). Download pdf

    Lu PD, Harding HP and Ron D. Translation re-initiation at alternative open reading frames regulates gene expression in an integrated stress response. J Cell Biol. 167:27-33 (2004). Download pdf

    Yoneda T, Benedetti C, Urano F, Clark SG, Harding HP and Ron D. Compartment specific perturbation of protein folding activates genes encoding mitochondrial chaperones.J Cell Sci. 117:4055-4066 (2004). Download pdf

    Lu PD, Jousse C, Marciniak SJ, Zhang Y, Novoa I, Scheuner D, Kaufman RJ, Ron D and Harding HP. Cytoprotection by pre-emptive conditional phosphorylation of translation initiation factor 2. EMBO J. 23:169-179 (2004). Download pdf

    Jousse C, Oyadomari S, Novoa I, Lu PD, Zhang Y, Harding HP and Ron D. Inhibition of a constitutive translation initiation factor 2alpha phosphatase, CReP, promotes survival of stressed cells. J Cell Biol. 163:767-775 (2003). Download pdf

    Novoa I, Zhang Y, Zeng H, Jungreis R, Harding HP and Ron D. Stress-induced gene expression requires programmed recovery from translational repression. EMBO J. 22:1180-1187 (2003). Download pdf

    Harding H, Zhang Y, Zeng H, Novoa I, Lu P, Calfon M, Sadri N, Yun C, Popko B, Paules R, Stojdl D, Bell J, Hettmann T, Leiden J and Ron D. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Molecular Cell 11:619-633 (2003). Download pdf Also see commentary by Rutkowski & Kaufman. "All Roads Lead to ATF4": Dev Cell 4:442-4 (2003).

    Calfon M., Zeng H., Urano F., Till J.H., Hubbard S.R., Harding H.P., Clark S.G. and Ron D. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415:92-96 (2002). Download pdf

    Urano F, Calfon M, Yoneda T, Yun C, Duke K, Kirali M, Clark SG and Ron D. A survival pathway for C. elegans with a blocked unfolded protein response. J Cell Biol. 158:639-646 (2002). Download pdf

    Bertolotti, A., Wang, X., Novoa, I., Jungreis, R., Schlessinger, K., Cho, J.H., West, A. B. and Ron D. Increased sensitivity to dextran sodium sulfate colitis in IRE1β deficient mice J Clin Invest 107:585-593 (2001). Download pdf

    Sok, J., Calfon, M., Jinyu, L., Lichtlen, P., Clark, S.G. and Ron D. Arsenite-inducible RNA-associated protein (AIRAP) protects cells from arsenite toxicity Cell Stress & Chaperones 6:6-15 (2001). Download pdf

    Novoa, I., Zeng, H., Harding, H.P., and Ron, D. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2α J Cell Biol 153: 1011-1021 (2001). Download pdf Also see the accompanying "in brief" commentary)

    Harding, H.P., Zeng, H., Zhang, Y., Jungries, R., Chung, P., Plesken, H., Sabatini, D.D. and Ron, D. Diabetes mellitus and exocrine pancreatic dysfunction in Perk-/- mice reveals a role for translational control in survival of secretory cells. Molecular Cell 7: 1153-1163 (2001). Download pdf

    Bertolotti, A., and Ron, D. Alterations in an IRE1-RNA complex in the mammalian unfolded protein response. J Cell Sci 114:3207-3212 (2001). Download pdf

    Urano, F., Wang, X., Bertolotti, A., Zhang, Y., Chung, P., Harding, H.P. and Ron, D. Coupling of Stress in the Endoplasmic Reticulum to Activation of JNK Protein Kinases by Transmembrane Protein Kinase IRE1. Science 287:664-666 (2000). Download pdf

    Kuroda, M., Sok, J., Webb, L., Baechtold, H., Urano, F., Yin, Y., Chung, P., Akhmedov, A., de Rooij, D.G., Ashley, T. and Ron, D. Male sterility and enhanced radiation sensitivity in TLS-/- mice. EMBO J 19:453-462 (2000). Download pdf

    Harding, H., Novoa, I., Zhang, Y., Zeng, H., Schapira, M., and Ron, D. Regulated translation initiation controls stress-induced gene expression in mammalian cells. Molecular Cell 6: 1099-1108 (2000). Download PDF

    Bertolotti, A., Zhang, Y., Hendershot, L.M., Harding, H.P., and Ron, D. Dynamic interaction of BiP and the ER stress transducers in the unfolded protein response. Nature Cell Biology 2: 326-332 (2000). Download pdf

    Harding, H.P., Zhang, Y., Bertolotti, A., Zeng, H., and Ron, D. Perk is essential for translational regulation and cell survival during the unfolded protein response. Molecular Cell 5: 897-904 (2000). Download pdf

    Harding HP, Zhang Y and Ron D. Translation and protein folding are coupled by an endoplasmic reticulum kinase. Nature 397:271-274 (1999). Download pdf. Also see accompanying commentary.

    Kuroda, M., Wang, X., Sok, J., Yin, Y., Chung, P., Giannotti, J., Jacobs, K.A., Fitz, L.J., Murtha-Riel, P., Turner, K.J. and Ron, D. Induction of a secreted protein by the myxoid liposarcoma oncogene. Proc. Natl. Acad. Sci. USA 96:5025-5030 (1999). Download pdf

    Zinszner, H. et al. CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev 12, 982-995 (1998). Download pdf

    Wang, X.-Z. et al. Identification of novel stress-induced genes downstream of chop. EMBO J 17, 3619-3630 (1998). Download pdf

    Wang, X.-Z., Harding, H., Zhang, Y., Jolicoeur, E. & Ron, D. Cloning of mammalian Ire1 reveals diversity in the ER stress responses. EMBO J 17, 5708-5717 (1998). Download pdf

    Wang, X.-Z. et al. Signals from the stressed endoplasmic reticulum induce C/EBP homologous protein (CHOP/GADD153). Mol Cell Biol 16, 4273-4280 (1996).

    Wang, X.-Z. & Ron, D. Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP-kinase. Science 272, 1347-1349 (1996). Download pdf

    Batchvarova, N., Wang, X.-Z. & Ron, D. Inhibition of adipogenesis by the stress-induced protein CHOP (GADD153). EMBO J. 14, 4654-4661 (1995).

    Crozat, A. Y., Aman, P., Mandahl, N. & Ron, D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma with t(12;16)(q13;p11). Nature 363, 640-644 (1993). Download pdf

    Ron, D. & Habener, J. F. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant negative inhibitor of gene transcription. Genes & Dev 6, 439-453 (1992). Download pdf

    Reviews and Commentaries:

    Volmer R and Ron D. 2015. Lipid-dependent regulation of the unfolded protein response. Current Opinion in Cell Biology 33: 67-73

    Ron D and Harding H.P. 2012. Protein-folding homeostasis in the endoplasmic reticulum and nutritional regulation. Cold Spring Harb Perspect Biol. Dec 1;4(12) (PMID: 23209157)

    Pavitt GD and Ron D. 2012. New insights into translational regulation in the endoplasmic reticulum unfolded protein response. Cold Spring Harb Perspect Biol. Jun 1;4(6) (PMID: 22535228)

    Walter P and Ron D. 2011. The unfolded protein response: From stress pathway to homeostatic regulation. Science 334:1081-6 (PMID: 22116877)

    Haynes CM and Ron D. 2010. The  mitochondrial UPR: Protecting organelle protein homeostasis. J Cell Science 123; 3849-55 (PMID: 21048161)

    Wiseman RL, Haynes CM and Ron D. 2010 Snapshot: The unfolded protein response. Cell 140:590- e2 (PMID: 20178750)

    Ron D. and Walter P. 2007. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 8:519-529. (Download PDF)

    Ron D. and Harding H.P. 2007. eIF2α phosphorylation in cellular stress-responses and disease.  In: Hershey JWB, Matthews MB, Sonenberg N, Eds. Translational Control in Biology and Medicine. Pages 345-368 (Chapter 13).  Cold Spring Harbor Press. (Download PDF)

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