GADD34

Summary

Gene Symbol: GADD34
Description: protein phosphatase 1 regulatory subunit 15A
Alias: GADD34, protein phosphatase 1 regulatory subunit 15A, growth arrest and DNA damage-inducible protein GADD34, growth arrest and DNA-damage-inducible 34, myeloid differentiation primary response protein MyD116 homolog, protein phosphatase 1, regulatory (inhibitor) subunit 15A
Species: human
Products:     GADD34

Top Publications

  1. Grishin A, Azhipa O, Semenov I, Corey S. Interaction between growth arrest-DNA damage protein 34 and Src kinase Lyn negatively regulates genotoxic apoptosis. Proc Natl Acad Sci U S A. 2001;98:10172-7 pubmed
    ..Among these molecules are the growth arrest and DNA damage protein 34 (GADD34) and the Src-related protein tyrosine kinase Lyn...
  2. Brush M, Shenolikar S. Control of cellular GADD34 levels by the 26S proteasome. Mol Cell Biol. 2008;28:6989-7000 pubmed publisher
    b>GADD34, the product of a growth arrest and DNA damage-inducible gene, is expressed at low levels in unstressed cells. In response to stress, the cellular content of GADD34 protein increases and, on termination of stress, rapidly declines...
  3. Lee Y, Cevallos R, Jan E. An upstream open reading frame regulates translation of GADD34 during cellular stresses that induce eIF2alpha phosphorylation. J Biol Chem. 2009;284:6661-73 pubmed publisher
    ..in turn induces transcription of downstream stress-induced genes such as growth arrest DNA-inducible gene 34 (GADD34)...
  4. Hollander M, Zhan Q, Bae I, Fornace A. Mammalian GADD34, an apoptosis- and DNA damage-inducible gene. J Biol Chem. 1997;272:13731-7 pubmed
    ..Induction of the human DNA damage- and growth arrest-inducible gene, GADD34, by ionizing radiation was only seen in certain cell lines and correlated with apoptosis following ionizing ..
  5. Brush M, Weiser D, Shenolikar S. Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. Mol Cell Biol. 2003;23:1292-303 pubmed
    The growth arrest and DNA damage-inducible protein, GADD34, associates with protein phosphatase 1 (PP1) and promotes in vitro dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2, (eIF-2 alpha)...
  6. Watanabe R, Tambe Y, Inoue H, Isono T, Haneda M, Isobe K, et al. GADD34 inhibits mammalian target of rapamycin signaling via tuberous sclerosis complex and controls cell survival under bioenergetic stress. Int J Mol Med. 2007;19:475-83 pubmed
    ..Here, we show that the expression of growth arrest and DNA damage protein 34 (GADD34) is induced by energy depletion and that the expression of this protein protects cells from apoptotic cell death...
  7. Nichols K, Doelman J, Kim J, Carson M, Metcalf J, Cant J. Exogenous essential amino acids stimulate an adaptive unfolded protein response in the mammary glands of lactating cows. J Dairy Sci. 2017;100:5909-5921 pubmed publisher
    ..the mRNA expression of genes encoding pro-apoptotic protein CHOP (C/EBP homologous protein) and downstream GADD34 (growth arrest and DNA damage-inducible 34)...
  8. Vieira F, Ping Q, Moreno A, Kidd J, Thompson K, Jiang B, et al. Guanabenz Treatment Accelerates Disease in a Mutant SOD1 Mouse Model of ALS. PLoS ONE. 2015;10:e0135570 pubmed publisher
    ..alpha2 adrenergic receptor agonist shown to interact with a regulatory subunit of the protein phosphatase, Pp1/Gadd34, and selectively disrupt the dephosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eif2alpha)...
  9. Sengupta S, Sevigny C, Bhattacharya P, Jordan V, Clarke R. Estrogen-Induced Apoptosis in Breast Cancers Is Phenocopied by Blocking Dephosphorylation of Eukaryotic Initiation Factor 2 Alpha (eIF2α) Protein. Mol Cancer Res. 2019;17:918-928 pubmed publisher
    ..using salubrinal to pharmacologically inhibit the enzymes responsible for dephosphorylation of eIF2α, GADD34, and CReP...

More Information

Publications142 found, 100 shown here

  1. Blas Valdivia V, Cano Europa E, Martínez Pérez Y, Lezama Palacios R, Franco Colin M, Ortiz Butron R. Hypothyroidism minimizes the effects of acute hepatic failure caused by endoplasmic reticulum stress and redox environment alterations in rats. Acta Histochem. 2015;117:811-9 pubmed publisher
    ..Furthermore, we measured reduced expressions of GADD34, caspase-12 and GRP78 and subsequently less hypothyroidism-induced cellular damage in hypothyroid animals...
  2. Kleber A, Ruf C, Wolf A, Fink T, Glas M, Wolf B, et al. Melatonin or ramelteon therapy differentially affects hepatic gene expression profiles after haemorrhagic shock in rat--A microarray analysis. Exp Mol Pathol. 2015;99:189-97 pubmed publisher
    ..The observed differences between both substances are likely to be attributable to a distinct mechanism of action in these agents. ..
  3. Tang Y, Wang Z, Yang J, Zheng W, Chen D, Wu G, et al. Polycystin-1 inhibits eIF2α phosphorylation and cell apoptosis through a PKR-eIF2α pathway. Sci Rep. 2017;7:11493 pubmed publisher
    ..Our TUNEL experiments using tunicamycin, an apoptosis inducer, and GADD34, an inhibitor of eIF2α phosphorylation, demonstrated that PC1-5TMC inhibits apoptosis of HEK293T cells in a PKR-..
  4. Hiraishi H, Oatman J, Haller S, Blunk L, McGivern B, Morris J, et al. Essential role of eIF5-mimic protein in animal development is linked to control of ATF4 expression. Nucleic Acids Res. 2014;42:10321-30 pubmed publisher
    ..In the red flour beetle, Tribolium castaneum, RNA interference studies indicate that 5MP facilitates expression of GADD34, a downstream target of ATF4. Furthermore, both 5MP and ATF4 are essential for larval development...
  5. Souliotis V, Vougas K, Gorgoulis V, Sfikakis P. Defective DNA repair and chromatin organization in patients with quiescent systemic lupus erythematosus. Arthritis Res Ther. 2016;18:182 pubmed publisher
    ..Approaches to correct these abnormalities may be of therapeutic value in SLE. ..
  6. Duprez J, Jonas J. Role of activating transcription factor 3 in low glucose- and thapsigargin-induced apoptosis in cultured mouse islets. Biochem Biophys Res Commun. 2011;415:294-9 pubmed publisher
    ..WT islets despite similar level of expression of Gadd153 and Gadd34 mRNA...
  7. van de Beek M, Ofman R, Dijkstra I, Wijburg F, Engelen M, Wanders R, et al. Lipid-induced endoplasmic reticulum stress in X-linked adrenoleukodystrophy. Biochim Biophys Acta Mol Basis Dis. 2017;1863:2255-2265 pubmed publisher
    ..fibroblasts to C26:0, resulted in increased expression of additional endoplasmic reticulum stress markers (EDEM1, GADD34 and CHOP) and in lipoapoptosis...
  8. Jiang M, Liu L, He X, Wang H, Lin W, Wang H, et al. Regulation of PERK-eIF2? signalling by tuberous sclerosis complex-1 controls homoeostasis and survival of myelinating oligodendrocytes. Nat Commun. 2016;7:12185 pubmed publisher
    ..Enhancement of the phospho-eIF2? adaptation pathway by inhibition of Gadd34-PP1 phosphatase with guanabenz protects oligodendrocytes and partially rescues myelination defects in Tsc1 mutants...
  9. Chequer F, Venâncio V, Almeida M, Aissa A, Bianchi M, Antunes L. Erythrosine B and quinoline yellow dyes regulate DNA repair gene expression in human HepG2 cells. Toxicol Ind Health. 2017;33:765-774 pubmed publisher
    ..In conclusion, our data suggest that the genotoxic mechanism of ErB and QY dyes involves the modulation of genes related to the DNA repair system and cell cycle. ..
  10. Tanaka K, Kawahara M. Copper Enhances Zinc-Induced Neurotoxicity and the Endoplasmic Reticulum Stress Response in a Neuronal Model of Vascular Dementia. Front Neurosci. 2017;11:58 pubmed publisher
    ..increased the expression of genes related to the endoplasmic reticulum's stress response, including CHOP, GADD34, and ATF4...
  11. Yu X, Xia W, Li S, Blumenfeld J, Zhang B, Yang J, et al. Antitumor effect and underlying mechanism of RGD-modified adenovirus mediated IL-24 expression on myeloid leukemia cells. Int Immunopharmacol. 2015;28:560-70 pubmed publisher
    ..Ad.RGD-IL-24 had a potent effect on the up-regulation of the expression of GRP78/Bip, GADD34 and Bax, down-regulation of the expression of Bcl-2 and Mcl-1, and induced the activation of Caspase-3, which may ..
  12. Moon S, Parker R. EIF2B2 mutations in vanishing white matter disease hypersuppress translation and delay recovery during the integrated stress response. RNA. 2018;24:841-852 pubmed publisher
    ..stress-induced gene expression and interrupting a negative feedback loop that allows translational recovery by GADD34-mediated dephosphorylation of phospho-eIF2?...
  13. Thiaville M, Pan Y, Gjymishka A, Zhong C, Kaufman R, Kilberg M. MEK signaling is required for phosphorylation of eIF2alpha following amino acid limitation of HepG2 human hepatoma cells. J Biol Chem. 2008;283:10848-57 pubmed publisher
    ..Inhibition of protein phosphatase 1 action on phospho-eIF2alpha by knockdown of GADD34 did not block the sensitivity to PD98059, suggesting that MEK functions to enhance GCN2-dependent eIF2alpha ..
  14. Aghaei M, Ghanadian M, Sajjadi S, Saghafian R, Keyvanloo Shahrestanaki M. Pimpinelol, a novel atypical Sesquiterpene lactone from Pimpinella haussknechtii fruits with evaluation of endoplasmic reticulum stress in breast cancer cells. Fitoterapia. 2018;129:198-202 pubmed publisher
    ..that Pimpinelol concentrations dependently increased protein aggregation and the mRNA expression of ATF-4, CHOP, GADD34 and TRIB3 in MCF-7 breast cancer cell line...
  15. Wu H, Wei L, Fan F, Ji S, Zhang S, Geng J, et al. Integration of Hippo signalling and the unfolded protein response to restrain liver overgrowth and tumorigenesis. Nat Commun. 2015;6:6239 pubmed publisher
    ..PERK kinase-eIF2α axis activates Yap, while prolonged ER stress-induced Hippo signalling triggers assembly of the GADD34/PP1 complex in a negative feedback loop to inhibit Yap and promote apoptosis...
  16. Melvin R, Lamichane N, Havula E, Kokki K, Soeder C, Jones C, et al. Natural variation in sugar tolerance associates with changes in signaling and mitochondrial ribosome biogenesis. elife. 2018;7: pubmed publisher
    ..that are involved in mitochondrial ribosome biogenesis and intracellular signaling, such as PPP1R15/Gadd34 and SERCA, which contributed to sugar tolerance...
  17. Hamzeloo Moghadam M, Aghaei M, Abdolmohammadi M, Khalaj A, Fallahian F. Cytotoxic effect of Drimia maritima bulb extract and induction of mitochondrial apoptotic signaling in human breast cancer cells, MCF-7 and MDA-MB-468. Onco Targets Ther. 2018;11:7669-7677 pubmed publisher
    ..dose-dependently increased the mRNA expression of ER stress markers such as CHOP, ATF-4, GADD34, and TRIB3 in MCF-7, and MDA-MB-468 cells. These data suggest that D...
  18. Hua K, Wang M, Chen M, Wei L, Chen C, Ko C, et al. The H3K9 methyltransferase G9a is a marker of aggressive ovarian cancer that promotes peritoneal metastasis. Mol Cancer. 2014;13:189 pubmed publisher
    ..Expression of these genes was also inversely correlated with G9a expression in OCa specimens. We propose that G9a contributes to multiple steps of ovarian cancer metastasis and represents a novel target to combat this deadly disease. ..
  19. Holzer M, Krähling V, Amman F, Barth E, Bernhart S, Carmelo V, et al. Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells. Sci Rep. 2016;6:34589 pubmed publisher
    ..We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections. ..
  20. Das I, Krzyzosiak A, Schneider K, Wrabetz L, D Antonio M, Barry N, et al. Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit. Science. 2015;348:239-42 pubmed publisher
    ..Thus, regulatory subunits of phosphatases are drug targets, a property exploited here to safely prevent two protein misfolding diseases. ..
  21. Chambers J, Dalton L, Clarke H, Malzer E, Dominicus C, Patel V, et al. Actin dynamics tune the integrated stress response by regulating eukaryotic initiation factor 2α dephosphorylation. elife. 2015;4: pubmed publisher
    ..G-actin's role as a stabilizer of the PPP1R15-containing holophosphatase provides a mechanism for integrating signals regulating actin dynamics with stresses that trigger the ISR. ..
  22. Zhao Y, Cao Q, He Y, Xue Q, Xie L, Yan Y. Impairment of endoplasmic reticulum is involved in ?-cell dysfunction induced by microcystin-LR. Environ Pollut. 2017;223:587-594 pubmed publisher
    ..ER stress significantly promoted the expression of PERK/eIF2? and their downstream targets (ATF4, CHOP, and Gadd34), which indicates that PERK-eIF2?-ATF4 pathway is involved in MC-LR-induced insulin deficiency...
  23. Zarcone M, Duistermaat E, van Schadewijk A, Jedyńska A, Hiemstra P, Kooter I. Cellular response of mucociliary differentiated primary bronchial epithelial cells to diesel exhaust. Am J Physiol Lung Cell Mol Physiol. 2016;311:L111-23 pubmed publisher
    ..Furthermore, DE significantly increased the expression of the markers of the integrated stress response CHOP and GADD34 and of the proinflammatory chemokine CXCL8, as well as release of CXCL8 protein...
  24. Kavaliauskis A, Arnemo M, Rishovd A, Gjøen T. Activation of unfolded protein response pathway during infectious salmon anemia virus (ISAV) infection in vitro an in vivo. Dev Comp Immunol. 2016;54:46-54 pubmed publisher
    ..This may be due to concomitant induction of an important negative feedback loop via the phosphatase regulator GADD34. The host cells can therefore respond with translation of cytokine and antiviral proteins to curb or control ..
  25. Otsuka R, Harada N, Aoki S, Shirai K, Nishitsuji K, Nozaki A, et al. C-terminal region of GADD34 regulates eIF2α dephosphorylation and cell proliferation in CHO-K1 cells. Cell Stress Chaperones. 2016;21:29-40 pubmed publisher
    b>GADD34 is a member of a growth arrest and DNA damage (GADD)-inducible gene family...
  26. Tan Z, Zhang W, Sun J, Fu Z, Ke X, Zheng C, et al. ZIKV infection activates the IRE1-XBP1 and ATF6 pathways of unfolded protein response in neural cells. J Neuroinflammation. 2018;15:275 pubmed publisher
    ..The transcriptional levels of atf4, gadd34, chop, and edem-1 in vivo and that of gadd34 and chop in vitro significantly increased...
  27. Moreno J, Radford H, Peretti D, Steinert J, Verity N, Martin M, et al. Sustained translational repression by eIF2α-P mediates prion neurodegeneration. Nature. 2012;485:507-11 pubmed publisher
    ..Overexpression of GADD34, a specific eIF2α-P phosphatase, as well as reduction of levels of prion protein by lentivirally mediated RNA ..
  28. Krajarng A, Imoto M, Tashiro E, Fujimaki T, Shinjo S, Watanapokasin R. Apoptosis induction associated with the ER stress response through up-regulation of JNK in HeLa cells by gambogic acid. BMC Complement Altern Med. 2015;15:26 pubmed publisher
    ..Markers of ER stress such as XBP-1, GRP78, CHOP, GADD34 and ERdj4 were analyzed by RT-PCR and Real-time RT-PCR...
  29. Kobylewski S, Henderson K, Yamada K, Eckhert C. Activation of the EIF2α/ATF4 and ATF6 Pathways in DU-145 Cells by Boric Acid at the Concentration Reported in Men at the US Mean Boron Intake. Biol Trace Elem Res. 2017;176:278-293 pubmed publisher
    ..by an increase in the expression of its downstream genes growth arrest and DNA damage-induced protein 34 (GADD34) and homocysteine-induced ER protein (Herp), but a decrease in GADD153/CCAAT/enhancer-binding protein homologous ..
  30. Nishio N, Isobe K. GADD34-deficient mice develop obesity, nonalcoholic fatty liver disease, hepatic carcinoma and insulin resistance. Sci Rep. 2015;5:13519 pubmed publisher
    ..DNA damage-inducible protein 34 (GADD34/Ppp1r15a), originally isolated from UV-inducible transcripts in Chinese hamster ovary (CHO) cells, ..
  31. Young S, Willy J, Wu C, Sachs M, Wek R. Ribosome Reinitiation Directs Gene-specific Translation and Regulates the Integrated Stress Response. J Biol Chem. 2015;290:28257-71 pubmed publisher
    ..Preferentially translated GADD34 (PPP1R15A) and constitutively expressed CReP (PPP1R15B) function to dephosphorylate eIF2α-P and restore protein ..
  32. D Antonio M, Musner N, Scapin C, Ungaro D, Del Carro U, Ron D, et al. Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice. J Exp Med. 2013;210:821-38 pubmed publisher
    ..Here, we show that Gadd34 is a detrimental effector of CHOP that reactivates translation too aggressively in myelinating Schwann cells...
  33. Panth K, Leijenaar R, Carvalho S, Lieuwes N, Yaromina A, Dubois L, et al. Is there a causal relationship between genetic changes and radiomics-based image features? An in vivo preclinical experiment with doxycycline inducible GADD34 tumor cells. Radiother Oncol. 2015;116:462-6 pubmed publisher
    ..HCT116 doxycycline (dox) inducible GADD34 cells were grown as xenografts in the flanks of NMRI-nu mice. GADD34 overexpression decreases hypoxic fraction...
  34. Dedigama Arachchige P, Acharige N, Pflum M. Identification of PP1-Gadd34 substrates involved in the unfolded protein response using K-BIPS, a method for phosphatase substrate identification. Mol Omics. 2018;14:121-133 pubmed publisher
    ..Then, as a further application, K-BIPS was used to discover the substrates of the PP1-Gadd34 phosphatase complex in the context of unfolded protein response (UPR)...
  35. Lin W, Lin Y, Li J, Harding H, Ron D, Jamison S. A deregulated integrated stress response promotes interferon-γ-induced medulloblastoma. J Neurosci Res. 2011;89:1586-95 pubmed publisher
    ..We found that inactivation of the growth arrest and DNA damage 34 (GADD34) gene, encoding the stress-inducible regulatory subunit of a phosphatase complex that dephosphorylates eIF2α, ..
  36. Liu L, Nishio N, Ito S, Tanaka Y, Isobe K. Negative regulation of GADD34 on myofibroblasts during cutaneous wound healing. Biomed Res Int. 2014;2014:137049 pubmed publisher
    The growth arrest and DNA damage-inducible protein, GADD34, has been proved to be involved in TGF-β signaling pathway and correlates with cell death, which are two important mechanisms in regulating myofibroblast differentiation and ..
  37. Hayakawa M, Itoh M, Ohta K, Li S, Ueda M, Wang M, et al. Quercetin reduces eIF2α phosphorylation by GADD34 induction. Neurobiol Aging. 2015;36:2509-18 pubmed publisher
    ..b>GADD34 induction was observed in the brain of wild-type mice, and APP23 mice fed quercetin in their diet...
  38. van t Wout E, van Schadewijk A, Lomas D, Stolk J, Marciniak S, Hiemstra P. Function of monocytes and monocyte-derived macrophages in α1-antitrypsin deficiency. Eur Respir J. 2015;45:365-76 pubmed publisher
    ..display an enhanced endoplasmic reticulum stress response upon a lipopolysaccharide trigger (XBP1 splicing, CHOP, GADD34 and GRP78 mRNA)...
  39. Zhao L, Zhao H, Qin W, Li G, Tang J, Wang J. [Role and mechanism of cAMP/Ca 2+ signal pathway in differentiation of bone marrow mesenchymal stem cells into neuronal cells induced by salidroside]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2017;34:401-408 pubmed publisher
  40. Boussabbeh M, Ben Salem I, Prola A, Guilbert A, Bacha H, Abid Essefi S, et al. Patulin induces apoptosis through ROS-mediated endoplasmic reticulum stress pathway. Toxicol Sci. 2015;144:328-37 pubmed publisher
    ..PAT activated endoplasmic reticulum (ER) and unfolded protein response as evidenced by up-regulation of GRP78 and GADD34, splicing of XBP1 mRNA, and expression of the proapoptotic factor CHOP...
  41. Nakashima H, Nguyen T, Kasai K, Passaro C, Ito H, Goins W, et al. Toxicity and Efficacy of a Novel GADD34-expressing Oncolytic HSV-1 for the Treatment of Experimental Glioblastoma. Clin Cancer Res. 2018;24:2574-2584 pubmed publisher
    ..5. These mutations suppress virus replication in nondividing brain neurons. NG34 expresses the human GADD34 gene under transcriptional control of a cellular Nestin gene promoter/enhancer element, whose expression ..
  42. Melas P, Qvist J, Deidda M, Upreti C, Wei Y, Sanna F, et al. Cannabinoid Modulation of Eukaryotic Initiation Factors (eIF2α and eIF2B1) and Behavioral Cross-Sensitization to Cocaine in Adolescent Rats. Cell Rep. 2018;22:2909-2923 pubmed publisher
    ..find that a cannabinoid receptor agonist (WIN 55,212-2 mesylate [WIN]) reduced p-eIF2α in vitro by upregulating GADD34 (PPP1R15A), the recruiter of protein phosphatase 1 (PP1)...
  43. Tsaytler P, Harding H, Ron D, Bertolotti A. Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis. Science. 2011;332:91-4 pubmed publisher
    ..We describe a small molecule, guanabenz, that bound to a regulatory subunit of protein phosphatase 1, PPP1R15A/GADD34, selectively disrupting the stress-induced dephosphorylation of the α subunit of translation initiation factor ..
  44. Birkenfeld A, Lee H, Majumdar S, Jurczak M, Camporez J, Jornayvaz F, et al. Influence of the hepatic eukaryotic initiation factor 2alpha (eIF2alpha) endoplasmic reticulum (ER) stress response pathway on insulin-mediated ER stress and hepatic and peripheral glucose metabolism. J Biol Chem. 2011;286:36163-70 pubmed publisher
    ..stress-dependent eIF2α-P pathway was inhibited by overexpressing a constitutively active C-terminal fragment of GADD34/PPP1R15a, a regulatory subunit of phosphatase that terminates ER stress signaling by phospho-eIF2α...
  45. Parzych K, Chinn T, Chen Z, Loaiza S, Porsch F, Valbuena G, et al. Inadequate fine-tuning of protein synthesis and failure of amino acid homeostasis following inhibition of the ATPase VCP/p97. Cell Death Dis. 2015;6:e2031 pubmed publisher
    ..Some of the proteotoxic effects of VCP depletion depended on the eIF2α phosphatase, protein phosphatase 1 regulatory subunit 15A (PPP1R15A)/PP1c, but not on mTORC1, although there appeared to be cross-talk between them...
  46. Dalet A, Argüello R, Combes A, Spinelli L, Jaeger S, Fallet M, et al. Protein synthesis inhibition and GADD34 control IFN-β heterogeneous expression in response to dsRNA. EMBO J. 2017;36:761-782 pubmed publisher
    ..arrest and then overcome this inhibition by decreasing eIF2α phosphorylation through phosphatase 1c cofactor GADD34 (Ppp1r15a) expression...
  47. Rekha R, Mily A, Sultana T, Haq A, Ahmed S, Mostafa Kamal S, et al. Immune responses in the treatment of drug-sensitive pulmonary tuberculosis with phenylbutyrate and vitamin D3 as host directed therapy. BMC Infect Dis. 2018;18:303 pubmed publisher
    ..Endoplasmic reticulum stress-related genes (GADD34 and XBP1spl) and human beta-defensin-1 (HBD1) gene expression were studied in monocyte-derived-macrophages (MDM) (..
  48. Sun X, Aimé P, Dai D, Ramalingam N, Crary J, Burke R, et al. Guanabenz promotes neuronal survival via enhancement of ATF4 and parkin expression in models of Parkinson disease. Exp Neurol. 2018;303:95-107 pubmed publisher
    ..The small molecule guanabenz enhances eIF2α phosphorylation by blocking the function of GADD34, a regulatory protein that promotes eIF2α dephosphorylation...
  49. Nishio N, Ito S, Isobe K. Loss of GADD34 induces early age-dependent deviation to the myeloid lineage. Immunol Cell Biol. 2014;92:170-80 pubmed publisher
    ..Upon aging, myeloid-biased HSCs are maintained, whereas lymphoid-biased HSCs are lost. GADD34 protein is expressed in myeloid-lineage cells and has been cloned from them...
  50. Malzer E, Szajewska Skuta M, Dalton L, Thomas S, Hu N, Skaer H, et al. Coordinate regulation of eIF2α phosphorylation by PPP1R15 and GCN2 is required during Drosophila development. J Cell Sci. 2013;126:1406-15 pubmed publisher
    ..Moreover, we show that its expression is necessary for embryonic and larval development and that this is to oppose the inhibitory effects of GCN2 on anabolic growth. ..
  51. Ohri S, Mullins A, Hetman M, Whittemore S. Inhibition of GADD34, the stress-inducible regulatory subunit of the endoplasmic reticulum stress response, does not enhance functional recovery after spinal cord injury. PLoS ONE. 2014;9:e109703 pubmed publisher
    ..Here, we investigated the contribution of stress-inducible PPP1R15A/GADD34, an ERSR signaling effector downstream of CHOP that dephosphorylates eIF2α, in the pathogenesis of SCI...
  52. Aveic S, Viola G, Accordi B, Micalizzi C, Santoro N, Masetti R, et al. Targeting BAG-1: a novel strategy to increase drug efficacy in acute myeloid leukemia. Exp Hematol. 2015;43:180-190.e6 pubmed publisher
    ..expression confirmed a decreased BCL-2 protein level but, in addition, provoked the increased transcription of GADD34 stress sensor...
  53. Crespillo Casado A, Chambers J, Fischer P, Marciniak S, Ron D. PPP1R15A-mediated dephosphorylation of eIF2α is unaffected by Sephin1 or Guanabenz. elife. 2017;6: pubmed publisher
    ..These findings challenge the view that [(o-chlorobenzylidene)amino]guanidines restore proteostasis by interfering with eIF2α-P dephosphorylation. ..
  54. Mazzio E, Lewis C, Soliman K. Transcriptomic Profiling of MDA-MB-231 Cells Exposed to Boswellia Serrata and 3-O-Acetyl-B-Boswellic Acid; ER/UPR Mediated Programmed Cell Death. Cancer Genomics Proteomics. 2017;14:409-425 pubmed
    ..XBP1, C/EBP homologous protein transcription factor (CHOP), ATF3 and DDIT3,4/DNA-damage-inducible transcript 3,4 (GADD34)...
  55. Li J, Cai X, Xia Q, Yao K, Chen J, Zhang Y, et al. Involvement of endoplasmic reticulum stress in all-trans-retinal-induced retinal pigment epithelium degeneration. Toxicol Sci. 2015;143:196-208 pubmed publisher
    ..Expression levels of ATF4, CHOP, and GADD34 in RPE cells increased in a concentration-dependent manner after incubation with atRAL...
  56. Lee J, Morrison W, Hollien J. Hairy and enhancer of split 1 (HES1) protects cells from endoplasmic reticulum stress-induced apoptosis through repression of GADD34. J Biol Chem. 2018;293:5947-5955 pubmed publisher
    ..u>arrest and DNA damage-inducible protein GADD34 (also known as Protein phosphatase 1 regulatory subunit 15A, or MyD116)...
  57. Crespillo Casado A, Claes Z, Choy M, Peti W, Bollen M, Ron D. A Sephin1-insensitive tripartite holophosphatase dephosphorylates translation initiation factor 2α. J Biol Chem. 2018;293:7766-7776 pubmed publisher
    ..Furthermore, none of the PPP1R15A-containing holophosphatases tested were inhibited by Sephin1 or guanabenz. ..
  58. Chen N, Nishio N, Ito S, Tanaka Y, Sun Y, Isobe K. Growth arrest and DNA damage-inducible protein (GADD34) enhanced liver inflammation and tumorigenesis in a diethylnitrosamine (DEN)-treated murine model. Cancer Immunol Immunother. 2015;64:777-89 pubmed publisher
    Growth arrest and DNA damage-inducible protein (GADD34/Ppp1r15a) is induced by various stimuli including DNA damage and ER stress...
  59. Ben Salem I, Prola A, Boussabbeh M, Guilbert A, Bacha H, Lemaire C, et al. Activation of ER stress and apoptosis by α- and β-zearalenol in HCT116 cells, protective role of Quercetin. Neurotoxicology. 2016;53:334-342 pubmed publisher
    ..stress and activated the Unfolded Protein Response (UPR) as evidenced by XBP1 mRNA splicing and up-regulation of GADD34, GRP78, ATF4 and CHOP...
  60. Young S, Shao Y, Bidwell J, Wek R. Nuclear Matrix Protein 4 Is a Novel Regulator of Ribosome Biogenesis and Controls the Unfolded Protein Response via Repression of Gadd34 Expression. J Biol Chem. 2016;291:13780-8 pubmed publisher
    ..eIF2?-P also induces a feedback mechanism through enhanced transcriptional and translational expression of Gadd34 (Ppp1r15A),which targets type 1 protein phosphatase for dephosphorylation of eIF2?-P to restore protein synthesis...
  61. Teoh P, Bi C, Sintosebastian C, Tay L, Fonseca R, Chng W. PRIMA-1 targets the vulnerability of multiple myeloma of deregulated protein homeostasis through the perturbation of ER stress via p73 demethylation. Oncotarget. 2016;7:61806-61819 pubmed publisher
    ..UPR markers, HSP70, CHOP and GADD34, were significantly up-regulated, concomitantly with the induction of apoptosis...
  62. Roidl D, Hellbach N, Bovio P, Villarreal A, Heidrich S, Nestel S, et al. DOT1L Activity Promotes Proliferation and Protects Cortical Neural Stem Cells from Activation of ATF4-DDIT3-Mediated ER Stress In Vitro. Stem Cells. 2016;34:233-45 pubmed publisher
    ..Although downstream effectors of the UPR, such as Ppp1r15a/Gadd34, Atf3, and Tnfrsf10b/Dr5 were also transcriptionally activated, this most likely occurred in response to increased ..
  63. Lenox A, Bhootada Y, Gorbatyuk O, FULLARD R, Gorbatyuk M. Unfolded protein response is activated in aged retinas. Neurosci Lett. 2015;609:30-5 pubmed publisher
    ..Using western blotting, we determined that the hallmarks of the UPR PERK arm, phosphorylated (p) eIF2a, ATF4, and GADD34, were significantly altered in aged vs. young rat retinas...
  64. Reid D, Tay A, Sundaram J, Lee I, Chen Q, George S, et al. Complementary Roles of GADD34- and CReP-Containing Eukaryotic Initiation Factor 2? Phosphatases during the Unfolded Protein Response. Mol Cell Biol. 2016;36:1868-80 pubmed publisher
    ..Two eIF2? phosphatases, containing GADD34 and CReP, catalyze P-eIF2? dephosphorylation...
  65. Stone S, Ho Y, Li X, Jamison S, Harding H, Ron D, et al. Dual role of the integrated stress response in medulloblastoma tumorigenesis. Oncotarget. 2016;7:64124-64135 pubmed publisher
    ..eIF2α is quickly dephosphorylated by the protein phosphatase 1 and growth arrest and DNA damage 34 (GADD34) complex. Data indicate that the ISR can either promote or suppress tumor development...
  66. Perego J, Mendes A, Bourbon C, Camosseto V, Combes A, Liu H, et al. Guanabenz inhibits TLR9 signaling through a pathway that is independent of eIF2α dephosphorylation by the GADD34/PP1c complex. Sci Signal. 2018;11: pubmed publisher
    ..Upon the resolution of ER stress, the inducible phosphatase 1 cofactor GADD34 promotes the dephosphorylation of the initiation factor eIF2α, thereby enabling protein translation to resume...
  67. Palam L, Gore J, Craven K, Wilson J, Korc M. Integrated stress response is critical for gemcitabine resistance in pancreatic ductal adenocarcinoma. Cell Death Dis. 2015;6:e1913 pubmed publisher
    ..revealed that Gem caused repression of global translation and this effect was reversed by ISRIB or by expressing GADD34 to facilitate eIF2 dephosphorylation...
  68. Ito S, Tanaka Y, Oshino R, Okado S, Hori M, Isobe K. GADD34 suppresses lipopolysaccharide-induced sepsis and tissue injury through the regulation of macrophage activation. Cell Death Dis. 2016;7:e2219 pubmed publisher
    Growth arrest and DNA damage inducible protein 34 (GADD34) is induced by various cellular stresses, such as DNA damage, endoplasmic reticulum stress, and amino-acid deprivation...
  69. Zarcone M, Duistermaat E, Alblas M, van Schadewijk A, Ninaber D, Clarijs V, et al. Effect of diesel exhaust generated by a city bus engine on stress responses and innate immunity in primary bronchial epithelial cell cultures. Toxicol In Vitro. 2018;48:221-231 pubmed publisher
    ..In contrast, expression of the stress-induced PPP1R15A/GADD34 and the chemokine CXCL8 was increased in cells exposed to DE and NTHi...
  70. Liu L, Ito S, Nishio N, Sun Y, Chen N, Tanaka Y, et al. GADD34 Facilitates Cell Death Resulting from Proteasome Inhibition. Anticancer Res. 2015;35:5317-24 pubmed
    ..To investigate the role of GADD34 in cell death following proteasome inhibition, we treated WT MEF and GADD34 KO MEF with MG132 and various analyses ..
  71. Sidoli M, Musner N, Silvestri N, Ungaro D, D Antonio M, Cavener D, et al. Ablation of Perk in Schwann Cells Improves Myelination in the S63del Charcot-Marie-Tooth 1B Mouse. J Neurosci. 2016;36:11350-11361 pubmed
    ..Inhibition of the eIF2? holophosphatase GADD34:PP1, increases the phosphorylation of eIF2? in Schwann cells and largely rescues S63del neuropathy...
  72. Zarcone M, van Schadewijk A, Duistermaat E, Hiemstra P, Kooter I. Diesel exhaust alters the response of cultured primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD) to non-typeable Haemophilus influenzae. Respir Res. 2017;18:27 pubmed publisher
    ..5-2-fold and GADD34, 1.5-fold) in cells from both COPD patients and controls...
  73. Shigemi Z, Manabe K, Hara N, Baba Y, Hosokawa K, Kagawa H, et al. Methylseleninic acid and sodium selenite induce severe ER stress and subsequent apoptosis through UPR activation in PEL cells. Chem Biol Interact. 2017;266:28-37 pubmed publisher
    ..The expression of UPR-related molecules (GRP78 and GADD34) and pro-apoptotic UPR molecules (CHOP, Bim, or Puma) were augmented in PEL cells treated with MSA or SS...
  74. Shelkovnikova T, Dimasi P, Kukharsky M, An H, Quintiero A, Schirmer C, et al. Chronically stressed or stress-preconditioned neurons fail to maintain stress granule assembly. Cell Death Dis. 2017;8:e2788 pubmed publisher
    ..This is due to upregulation of PP1 phosphatase regulatory subunits GADD34 and/or CReP in preconditioned cells and early decline of p-eIF2α levels during subsequent acute stress...
  75. Ben Salem I, Prola A, Boussabbeh M, Guilbert A, Bacha H, Abid Essefi S, et al. Crocin and Quercetin protect HCT116 and HEK293 cells from Zearalenone-induced apoptosis by reducing endoplasmic reticulum stress. Cell Stress Chaperones. 2015;20:927-38 pubmed publisher
    ..activates the unfolded protein response (UPR) as evidenced by XBP1 mRNA splicing and upregulation of GRP78, ATF4, GADD34, PDIA6, and CHOP...
  76. Nustede R, Klimiankou M, Klimenkova O, Kuznetsova I, Zeidler C, Welte K, et al. ELANE mutant-specific activation of different UPR pathways in congenital neutropenia. Br J Haematol. 2016;172:219-27 pubmed publisher
    ..In summary, different ELANE mutants have different effects on UPR activation, and SLPI regulates the extent of ELANE-triggered UPR. ..
  77. Bahar E, Lee G, Bhattarai K, Lee H, Choi M, Rashid H, et al. Polyphenolic Extract of Euphorbia supina Attenuates Manganese-Induced Neurotoxicity by Enhancing Antioxidant Activity through Regulation of ER Stress and ER Stress-Mediated Apoptosis. Int J Mol Sci. 2017;18: pubmed publisher
    ..Meanwhile, PPEES pretreatment significantly reversed the Mn-induced alteration in the GRP78, GADD34, XBP-1, CHOP, Bcl-2, Bax and caspase-3 activities...
  78. Liao Y, Gu F, Mao X, Niu Q, Wang H, Sun Y, et al. Regulation of de novo translation of host cells by manipulation of PERK/PKR and GADD34-PP1 activity during Newcastle disease virus infection. J Gen Virol. 2016;97:867-79 pubmed publisher
    ..levels of phospho-eIF2α led to preferential translation of the transcription factor ATF4 and an increase in GADD34 expression...
  79. Ben Salem I, Boussabbeh M, Prola A, Guilbert A, Bacha H, Lemaire C, et al. Crocin protects human embryonic kidney cells (HEK293) from ?- and ?-Zearalenol-induced ER stress and apoptosis. Environ Sci Pollut Res Int. 2016;23:15504-14 pubmed publisher
    ..of the 78 kDa glucose-regulated protein (GRP78) and the Growth arrest and DNA damage-inducible protein (GADD34). Activation of the ER stress response is associated with activation of the mitochondrial pathway of apoptosis...
  80. Trzepizur W, Khalyfa A, Qiao Z, Popko B, Gozal D. Integrated stress response activation by sleep fragmentation during late gestation in mice leads to emergence of adverse metabolic phenotype in offspring. Metabolism. 2017;69:188-198 pubmed publisher
    ..We hypothesized that adult offspring of double mutant mice (DM) involving the critical ISR genes CHOP and GADD34 would be protected from developing obesity and insulin resistance following SF...
  81. Ma J, Yang Y, Chen W, Chen M, Wang H, Wang X, et al. Fluoxetine synergizes with temozolomide to induce the CHOP-dependent endoplasmic reticulum stress-related apoptosis pathway in glioma cells. Oncol Rep. 2016;36:676-84 pubmed publisher
    ..This induction was associated with activation of the PERK-eIF2?-ATF4 and ATF6 cascade. Concomitantly, GADD34, a downstream molecule of CHOP, was also increased...
  82. Morton E, Macrae I, McCabe C, Brown S, White F. Identification of the growth arrest and DNA damage protein GADD34 in the normal human heart and demonstration of alterations in expression following myocardial ischaemia. Int J Cardiol. 2006;107:126-9 pubmed
    Growth arrest and DNA damage protein 34 (GADD34) is a multifunctional protein upregulated in response to cellular stress and is believed to mediate DNA repair and restore protein synthesis...
  83. Clavarino G, Adriouach S, Quesada J, Clay M, Chevreau M, Trocmé C, et al. Unfolded protein response gene GADD34 is overexpressed in rheumatoid arthritis and related to the presence of circulating anti-citrullinated protein antibodies. Autoimmunity. 2016;49:172-8 pubmed publisher
    Growth arrest and DNA damage-inducible gene 34 (GADD34) is an inducible cofactor of protein phosphatase 1, which has an important role in the unfolded protein response...
  84. Liu L, Ito S, Nishio N, Sun Y, Tanaka Y, Isobe K. GADD34 Promotes Tumor Growth by Inducing Myeloid-derived Suppressor Cells. Anticancer Res. 2016;36:4623-8 pubmed
    Tumor hypoxia induces the expression of growth arrest and DNA damage-inducible protein (GADD34). However, the role of GADD34 in tumor growth remains unclear...
  85. Andreev D, O Connor P, Fahey C, Kenny E, Terenin I, Dmitriev S, et al. Translation of 5' leaders is pervasive in genes resistant to eIF2 repression. elife. 2015;4:e03971 pubmed publisher
    ..Phylogenetic analysis suggests that at least two regulatory uORFs (namely, in SLC35A4 and MIEF1) encode functional protein products. ..
  86. Roh S, Park I, Yoon Y, Kwon Y, Chung J, Kim T, et al. Feasibility of novel PPP1R15A and proposed ANXA11 single nucleotide polymorphisms as predictive markers for bevacizumab regimen in metastatic colorectal cancer. J Cancer Res Clin Oncol. 2016;142:1705-14 pubmed publisher
    ..001 and 0.026, respectively). ANXA11 rs1049550 and PPP1R15A rs557806 may improve the identification of mCRC patients sensitive to bevacizumab regimens, and further validation is required in large cohorts. ..
  87. Wu D, Tkachuck D, Roberson R, Schubach W. The human SNF5/INI1 protein facilitates the function of the growth arrest and DNA damage-inducible protein (GADD34) and modulates GADD34-bound protein phosphatase-1 activity. J Biol Chem. 2002;277:27706-15 pubmed
    The growth arrest and DNA damage-inducible protein (GADD34) mediates growth arrest and apoptosis in response to DNA damage, negative growth signals, and protein malfolding...
  88. Shi W, Sun C, He B, Xiong W, Shi X, Yao D, et al. GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. J Cell Biol. 2004;164:291-300 pubmed
    ..We found Smad7 interacts with growth arrest and DNA damage protein, GADD34, a regulatory subunit of the protein phosphatase 1 (PP1) holoenzyme, which subsequently recruits catalytic subunit ..
  89. Mukai R, Ohshima T. HTLV-1 HBZ positively regulates the mTOR signaling pathway via inhibition of GADD34 activity in the cytoplasm. Oncogene. 2014;33:2317-28 pubmed publisher
    ..target of rapamycin (mTOR) signaling pathway through an association with growth arrest and DNA damage gene 34 (GADD34). The N-terminal region of HBZ interacts with the C-terminal region of GADD34...
  90. Oh hashi K, Sugiura N, Amaya F, Isobe K, Hirata Y. Functional validation of ATF4 and GADD34 in Neuro2a cells by CRISPR/Cas9-mediated genome editing. Mol Cell Biochem. 2018;440:65-75 pubmed publisher
    ..Further, growth arrest and DNA damage-inducible gene 34 (GADD34), a downstream target of ATF4, has been reported to negatively regulate ATF4 expression...
  91. Ren Z, Chen S, Qing T, Xuan J, Couch L, Yu D, et al. Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017;392:11-21 pubmed publisher
    ..activated an unfolded protein response, as evidenced by increased expression of related genes including CHOP and GADD34; and elevated protein levels of typical ER stress markers including CHOP, ATF-4, p-eIF2?, and spliced XBP1...
  92. Salah A, Bouaziz C, Prola A, Pires Da Silva J, Bacha H, Abid Essefi S, et al. Citrinin induces apoptosis in human HCT116 colon cancer cells through endoplasmic reticulum stress. J Toxicol Environ Health A. 2017;80:1230-1241 pubmed publisher
    ..by increase in expression of GRP78 (glucose-regulated protein-78), GRP94 (glucose-regulated protein-94), GADD34 (growth arrest and DNA damage-inducible protein-34), the protein disulfide isomerase associated 6 (PDIA6), CHOP (C/..