Gene Symbol: Ppp1r15a
Description: protein phosphatase 1, regulatory subunit 15A
Alias: Gadd34, Myd116, Peg-3, RGD1624209, protein phosphatase 1 regulatory subunit 15A, growth arrest and DNA damage-inducible protein GADD34, myeloid differentiation primary response gene 116, myeloid differentiation primary response protein MyD116 homolog, progression elevated gene 3 protein, protein phosphatase 1, regulatory (inhibitor) subunit 15A
Species: rat
Products:     Ppp1r15a

Top Publications

  1. Jayanthi S, McCoy M, Beauvais G, Ladenheim B, Gilmore K, Wood W, et al. Methamphetamine induces dopamine D1 receptor-dependent endoplasmic reticulum stress-related molecular events in the rat striatum. PLoS ONE. 2009;4:e6092 pubmed publisher
    ..We also measured the expression of these genes and of ATF4, ATF6, BiP/GRP78, and of GADD34 over a more extended time course...
  2. Novoa I, Zeng H, Harding H, Ron D. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. J Cell Biol. 2001;153:1011-22 pubmed
    ..eIF2alpha kinases PERK (also known as PEK) and GCN2, phospho-eIF2alpha levels were markedly diminished in GADD34-overexpressing cells...
  3. Penas C, Guzmán M, Verdú E, Forés J, Navarro X, Casas C. Spinal cord injury induces endoplasmic reticulum stress with different cell-type dependent response. J Neurochem. 2007;102:1242-55 pubmed
    ..of alpha subunit of eukaryotic initiation factor 2 soon restored by the up-regulation of its regulator Gadd34; an effective cleavage/activation of the ATF6alpha transcription factor leading to up-regulation of the canonical ..
  4. Doutheil J, Althausen S, Gissel C, Paschen W. Activation of MYD116 (gadd34) expression following transient forebrain ischemia of rat: implications for a role of disturbances of endoplasmic reticulum calcium homeostasis. Brain Res Mol Brain Res. 1999;63:225-32 pubmed
    MyD116 is the murine homologue of growth arrest- and DNA damage-inducible genes (gadd34), a gene family implicated in growth arrest and apoptosis induced by endoplasmic reticulum dysfunction...
  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. Marciniak S, Yun C, Oyadomari S, Novoa I, Zhang Y, Jungreis R, et al. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 2004;18:3066-77 pubmed
    ..We find that CHOP directly activates GADD34, which promotes ER client protein biosynthesis by dephosphorylating phospho-Ser 51 of the alpha-subunit of ..
  7. Hyrskyluoto A, Reijonen S, Kivinen J, Lindholm D, Korhonen L. GADD34 mediates cytoprotective autophagy in mutant huntingtin expressing cells via the mTOR pathway. Exp Cell Res. 2012;318:33-42 pubmed publisher
    ..Tuberous sclerosis complex (TSC) 1/2 interacted with growth arrest and DNA damage protein 34 (GADD34), which caused TSC2 dephosphorylation and induction of autophagy in mutant huntingtin expressing cells...
  8. 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)...
  9. Hussain S, Ramaiah K. Reduced eIF2alpha phosphorylation and increased proapoptotic proteins in aging. Biochem Biophys Res Commun. 2007;355:365-70 pubmed
    ..Decline in eIF2alpha phosphorylation in aged tissues is associated with a higher level of GADD34, a subunit of eIF2alpha phosphatase, and proapoptotic proteins like CHOP/GADD153 and phospho JNK, suggesting that ..

More Information


  1. Ma J, Qiu Y, Yang L, Peng L, Xia Z, Hou L, et al. Desipramine induces apoptosis in rat glioma cells via endoplasmic reticulum stress-dependent CHOP pathway. J Neurooncol. 2011;101:41-8 pubmed publisher
    ..elevated expression of endoplasmic reticulum stress regulator CHOP/GADD153 and its targeting molecule GADD34. However, knockdown of CHOP by CHOP-specific short interfering RNA (siRNA) could decrease the activity of ..
  2. Hollander M, Poola Kella S, Fornace A. Gadd34 functional domains involved in growth suppression and apoptosis. Oncogene. 2003;22:3827-32 pubmed
    Gadd34 (also known as MyD116) was originally described as a growth arrest and DNA damage-inducible gene...
  3. Su Z, Emdad L, Sarkar D, Randolph A, Valerie K, Yacoub A, et al. Potential molecular mechanism for rodent tumorigenesis: mutational generation of Progression Elevated Gene-3 (PEG-3). Oncogene. 2005;24:2247-55 pubmed
    ..PEG-3 originates from mutation in the growth arrest and DNA damage inducible gene GADD34. A one base deletion in rat GADD34 results in a frame-shift and premature appearance of a stop-codon resulting in ..
  4. Kitamura M, Kato H, Saito Y, Nakajima S, Takahashi S, Johno H, et al. Aberrant, differential and bidirectional regulation of the unfolded protein response towards cell survival by 3'-deoxyadenosine. Cell Death Differ. 2011;18:1876-88 pubmed publisher
    ..It was associated with depression of GADD34 that dephosphorylates eIF2?, and dephosphorylation of eIF2? by salubrinal mimicked the anti-apoptotic effect of 3'-..
  5. McCaig D, Imai H, Gallagher L, Graham D, Harland J, Moira Brown S, et al. Evolution of GADD34 expression after focal cerebral ischaemia. Brain Res. 2005;1034:51-61 pubmed
    b>GADD34, a stress response protein associated with cell rescue, DNA repair and apoptosis, is expressed in the ischaemic brain. The C-terminal region of GADD34 has homology with the Herpes Simplex Virus protein, ICP34...
  6. Kitaguchi Y, Taraseviciene Stewart L, Hanaoka M, Natarajan R, Kraskauskas D, Voelkel N. Acrolein induces endoplasmic reticulum stress and causes airspace enlargement. PLoS ONE. 2012;7:e38038 pubmed publisher
    ..Here we test the hypothesis whether systemic administration of acrolein could cause endoplasmic reticulum (ER) stress, and lung cell apoptosis, leading to the enlargement of the alveolar air spaces in rats...
  7. Su Z, Goldstein N, Jiang H, Wang M, Duigou G, Young C, et al. PEG-3, a nontransforming cancer progression gene, is a positive regulator of cancer aggressiveness and angiogenesis. Proc Natl Acad Sci U S A. 1999;96:15115-20 pubmed
    ..In these contexts, PEG-3 may represent an important target molecule for developing cancer therapeutics and inhibitors of angiogenesis. ..
  8. Badiola N, Penas C, Miñano Molina A, Barneda Zahonero B, Fadó R, Sánchez Opazo G, et al. Induction of ER stress in response to oxygen-glucose deprivation of cortical cultures involves the activation of the PERK and IRE-1 pathways and of caspase-12. Cell Death Dis. 2011;2:e149 pubmed publisher
    ..Activation of PERK led to a transient phosphorylation of eIF2?, an increase in ATF4 levels and the induction of gadd34 (a subunit of an eIF2?-directed phosphatase)...
  9. Lum C, Yang Z, Li H, Wai Yin Sun R, Fan S, Poon R, et al. Gold(III) compound is a novel chemocytotoxic agent for hepatocellular carcinoma. Int J Cancer. 2006;118:1527-38 pubmed
    ..particular, the compound upregulated 2 members of the growth arrest and DNA damage (Gadd) inducible gene family, Gadd34 and Gadd153...
  10. 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
    ..Multiple isolates of GADD34 and the related murine protein MyD116 were identified as binding partners of Lyn in a yeast two-hybrid screen...
  11. Garcia Bonilla L, Cid C, Alcazar A, Burda J, Ayuso I, Salinas M. Regulatory proteins of eukaryotic initiation factor 2-alpha subunit (eIF2 alpha) phosphatase, under ischemic reperfusion and tolerance. J Neurochem. 2007;103:1368-80 pubmed
    ..IT that promoted a decrease in eIF2alpha phosphorylated levels after 30 min reperfusion induced the association of GADD34 with PP1c, while prevented that of DARPP32, GRP78, and HSC70...
  12. Su Z, Shi Y, Fisher P. Subtraction hybridization identifies a transformation progression-associated gene PEG-3 with sequence homology to a growth arrest and DNA damage-inducible gene. Proc Natl Acad Sci U S A. 1997;94:9125-30 pubmed
    ..homology with the hamster growth arrest and DNA damage-inducible gene gadd34 and a homologous murine gene, MyD116, that is induced during induction of terminal differentiation by interleukin-6 in murine myeloid leukemia cells...
  13. Amundson S, Zhan Q, Penn L, Fornace A. Myc suppresses induction of the growth arrest genes gadd34, gadd45, and gadd153 by DNA-damaging agents. Oncogene. 1998;17:2149-54 pubmed
    ..These results indicate that a coordinate down-regulation of the gadd gene response is one mechanism by which Myc can circumvent growth arrest and contribute to the neoplastic phenotype. ..
  14. Beauvais G, Atwell K, Jayanthi S, Ladenheim B, Cadet J. Involvement of dopamine receptors in binge methamphetamine-induced activation of endoplasmic reticulum and mitochondrial stress pathways. PLoS ONE. 2011;6:e28946 pubmed publisher
    ..METH also caused up-regulation of ER-stress genes, Atf2, Atf3, Atf4, CHOP/Gadd153 and Gadd34. The expression of heat shock proteins (HSPs) was increased after METH injections...
  15. Lin W, Kunkler P, Harding H, Ron D, Kraig R, Popko B. Enhanced integrated stress response promotes myelinating oligodendrocyte survival in response to interferon-gamma. Am J Pathol. 2008;173:1508-17 pubmed publisher
    ..In this study, we found that growth arrest and DNA damage 34 (GADD34), a stress-inducible regulatory subunit of a phosphatase complex that dephosphorylates eIF2alpha, was selectively ..
  16. Connor J, Weiser D, Li S, Hallenbeck J, Shenolikar S. Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1. Mol Cell Biol. 2001;21:6841-50 pubmed publisher
    The growth arrest and DNA damage-inducible protein, GADD34, was identified by its interaction with human inhibitor 1 (I-1), a protein kinase A (PKA)-activated inhibitor of type 1 protein serine/threonine phosphatase (PP1), in a yeast two-..
  17. Mengesdorf T, Althausen S, Oberndorfer I, Paschen W. Response of neurons to an irreversible inhibition of endoplasmic reticulum Ca(2+)-ATPase: relationship between global protein synthesis and expression and translation of individual genes. Biochem J. 2001;356:805-12 pubmed
    ..The mRNA levels of genes responding to conditions of ER stress (grp78, grp94, gadd34 and gadd153) were increased up to 200-fold after Tg exposure, whereas those coding for ER-resident proteins (SERCA ..
  18. Szegezdi E, Herbert K, Kavanagh E, Samali A, Gorman A. Nerve growth factor blocks thapsigargin-induced apoptosis at the level of the mitochondrion via regulation of Bim. J Cell Mol Med. 2008;12:2482-96 pubmed publisher
    ..NGF had no effect on the TG-mediated induction of the unfolded protein response (increased expression of Grp78, GADD34, splicing of XBP1 mRNA) or ER stress-associated pro-apoptotic responses (induction of C/EBP homologous protein [..
  19. Grootjans J, Hodin C, de Haan J, Derikx J, Rouschop K, Verheyen F, et al. Level of activation of the unfolded protein response correlates with Paneth cell apoptosis in human small intestine exposed to ischemia/reperfusion. Gastroenterology. 2011;140:529-539.e3 pubmed publisher
    ..In addition, we investigated the consequences of Paneth cell compromise during physical barrier damage...
  20. Pavlovsky A, Boehning D, Li D, Zhang Y, Fan X, Green T. Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain. Neuroscience. 2013;246:160-9 pubmed publisher
    ..Restraint stress and cocaine-induced transcription of the classic ER stress-induced genes (BIP, CHOP, ATF3 and GADD34) and of two other ER stress components x-box binding protein 1 (XBP1) and ATF6...
  21. Emdad L, Sarkar D, Su Z, Boukerche H, Bar Eli M, Fisher P. Progression elevated gene-3 (PEG-3) induces pleiotropic effects on tumor progression: modulation of genomic stability and invasion. J Cell Physiol. 2005;202:135-46 pubmed
    ..These findings demonstrate that PEG-3 plays a central role in augmenting tumor progression by modulating several critical parameters of the carcinogenic process, such as genomic stability and local tumor cell invasion. ..
  22. Paschen W, Hayashi T, Saito A, Chan P. GADD34 protein levels increase after transient ischemia in the cortex but not in the CA1 subfield: implications for post-ischemic recovery of protein synthesis in ischemia-resistant cells. J Neurochem. 2004;90:694-701 pubmed
    ..Recovery from ER dysfunction is facilitated by GADD34, a protein that dephosphorylates eukaryotic initiation factor (eIF)2alpha-P and thus reactivates protein synthesis...
  23. Schug M, Stöber R, Heise T, Mielke H, Gundert Remy U, Godoy P, et al. Pharmacokinetics explain in vivo/in vitro discrepancies of carcinogen-induced gene expression alterations in rat liver and cultivated hepatocytes. Arch Toxicol. 2013;87:337-45 pubmed publisher
    ..alters the expression of the metabolizing genes SULT1A1 and ABAT, as well as the DNA damage response gene GADD34 in vitro, but not in vivo...
  24. Coustry F, Posey K, Liu P, Alcorn J, Hecht J. D469del-COMP retention in chondrocytes stimulates caspase-independent necroptosis. Am J Pathol. 2012;180:738-48 pubmed publisher
    ..Retention of D469del-COMP stimulated Chop (Ddit3) and Gadd34 (Ppp1r15a) and triggered reactivation of protein translation that exacerbated intracellular retention...
  25. Mohammad Gharibani P, Modi J, Menzie J, Genova R, Ma Z, Tao R, et al. Mode of action of S-methyl-N, N-diethylthiocarbamate sulfoxide (DETC-MeSO) as a novel therapy for stroke in a rat model. Mol Neurobiol. 2014;50:655-72 pubmed publisher
    ..Levels of the ER stress protein markers p-PERK, p-eIF2?, ATF4, JNK, XBP-1, GADD34, and CHOP significantly declined after DETC-MeSO administration...
  26. Lin M, Yen J, Weng C, Wang L, Ha C, Wu M. Lipid peroxidation end product 4-hydroxy-trans-2-nonenal triggers unfolded protein response and heme oxygenase-1 expression in PC12 cells: Roles of ROS and MAPK pathways. Toxicology. 2014;315:24-37 pubmed publisher
    ..PERK-eIF2?-ATF4 and ATF6, and induced the expression of UPR-targeted genes, GRP78, CHOP, TRB3, PUMA, and GADD34, as well as Phase II enzymes, HO-1 and GCLC...
  27. Jaronen M, Vehviläinen P, Malm T, Keksa Goldsteine V, Pollari E, Valonen P, et al. Protein disulfide isomerase in ALS mouse glia links protein misfolding with NADPH oxidase-catalyzed superoxide production. Hum Mol Genet. 2013;22:646-55 pubmed publisher
    ..The observation was supported by the finding that also the expression of a UPR marker GADD34 (growth arrest and DNA damage-inducible protein) was induced in the spinal cord glia of tg mutant SOD1 mice...
  28. Yagi A, Hasegawa Y, Xiao H, Haneda M, Kojima E, Nishikimi A, et al. GADD34 induces p53 phosphorylation and p21/WAF1 transcription. J Cell Biochem. 2003;90:1242-9 pubmed
    Recently, others and we have shown that one of the functions of GADD34 is a recovery from a shutoff of protein synthesis induced by endoplasmic reticulum stress. GADD34 has been shown to induce growth arrest and apoptosis...
  29. Zhou W, Brush M, Choy M, Shenolikar S. Association with endoplasmic reticulum promotes proteasomal degradation of GADD34 protein. J Biol Chem. 2011;286:21687-96 pubmed publisher
    Stress-induced endogenous and ectopically expressed GADD34 proteins were present both in the cytoplasm and in membranes, with their membrane association showing similar biochemical properties...
  30. Latreille M, Larose L. Nck in a complex containing the catalytic subunit of protein phosphatase 1 regulates eukaryotic initiation factor 2alpha signaling and cell survival to endoplasmic reticulum stress. J Biol Chem. 2006;281:26633-44 pubmed
    ..of eIF2alphaSer51 is accomplished by protein phosphatase 1 (PP1c) complexes containing either the protein CReP or GADD34, which target PP1c to eIF2...
  31. Lelong D, Bieche I, Perez E, Bigot K, Leemput J, Laurendeau I, et al. Novel mouse model of monocular amaurosis fugax. Stroke. 2007;38:3237-44 pubmed
    ..We created and characterized a mouse model of global and transient retinal ischemia and provide a comprehensive chronologic profile of some genes that display altered expression during ischemia...