{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPPP1R15A, also known as GADD34, is a stress‐inducible regulatory subunit of protein phosphatase 1 (PP1) that plays a key role in the integrated stress response (ISR). Under diverse stress conditions—including DNA damage, endoplasmic reticulum stress, oxidative stress, and exposure to viral or environmental insults—PPP1R15A is transcriptionally and translationally induced, thereby recruiting PP1 to dephosphorylate eukaryotic initiation factor 2α (eIF2α) and re‐initiate protein synthesis. This dephosphorylation event is critical for terminating the stress response and restoring normal cellular translation programs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic studies have revealed that PPP1R15A acts as a scaffold that independently binds both its catalytic partner PP1 and the substrate eIF2α through distinct regions. Structural and functional analyses demonstrate that evolutionarily conserved domains within PPP1R15A mediate substrate recruitment, while defined PP1‐binding motifs ensure the assembly of an efficient holoenzyme. These domains are essential for the selective dephosphorylation of eIF2α, thus fine‐tuning the balance between translational repression during stress and recovery afterwards."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various pathological settings, PPP1R15A is centrally involved in modulating cellular stress responses. Viral infections (such as by coronaviruses and enteroviruses) exploit PPP1R15A to counteract host defenses through enhanced eIF2α dephosphorylation, thereby sustaining viral protein synthesis. Similarly, in neurodegenerative diseases and ischemic injury, altered expression of PPP1R15A has been implicated in maladaptive stress responses, while in several cancers and inflammatory conditions, its regulatory activity can determine cell survival or apoptotic fate. These observations underscore the multifaceted contributions of PPP1R15A in cell homeostasis and disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, the cellular levels and activity of PPP1R15A are tightly regulated by post‐transcriptional and post‐translational mechanisms. Rapid protein turnover via N‐terminal degrons and polyubiquitination ensures that PPP1R15A levels decline promptly after stress resolution. Interactions with components such as cytoskeletal actin, acetylation events affecting its binding properties, and recruitment of additional factors (e.g., SIRT1) further modulate its phosphatase activity and substrate specificity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic polymorphisms and regulatory variations in the PPP1R15A gene have been linked to differential stress responsiveness and disease susceptibility. Studies report that specific single nucleotide polymorphisms (SNPs) correlate with heightened tumor risk, while alterations in its upstream regulatory pathways (involving JNK/c-Jun and interactions with viral oncoproteins) modulate its expression during pathogenic challenges. These findings suggest that PPP1R15A function and regulation may serve as promising diagnostic biomarkers and therapeutic targets in diverse human diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond simply ending the stress response, PPP1R15A is crucial for cellular adaptation by modulating key survival pathways. In response to various metabolic insults and nutrient deprivation, its activity helps synchronize the reactivation of protein synthesis with autophagy and mTOR signaling, thereby preserving cell viability during prolonged stress. This fine‐tuning of translation reactivation and autophagic flux illustrates the central role of PPP1R15A in maintaining proteostasis in dynamic environmental conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "29"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, PPP1R15A influences cell fate decisions by impacting apoptotic pathways and oncogenic signaling. By stabilizing key survival proteins and interacting with regulators of cell cycle and inflammation, it contributes to resistance against apoptosis in cancer models while also modulating responses to chemotherapeutic agents. These functions highlight its dual role as both a protector against unwarranted cell death and a potential contributor to oncogenic progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "30", "end_ref": "35"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Weibin Shi, Chuanxi Sun, Bin He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200307151"}], "href": "https://doi.org/10.1083/jcb.200307151"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14718519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14718519"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yun-Young Lee, Randal C Cevallos, Eric Jan "}, {"type": "b", "children": [{"type": "t", "text": "An upstream open reading frame regulates translation of GADD34 during cellular stresses that induce eIF2alpha phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M806735200"}], "href": "https://doi.org/10.1074/jbc.M806735200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19131336"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19131336"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Meng S Choy, Permeen Yusoff, Irene C Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural and Functional Analysis of the GADD34:PP1 eIF2α Phosphatase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2015.05.043"}], "href": "https://doi.org/10.1016/j.celrep.2015.05.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26095357"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26095357"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Margarito Rojas, Gabriel Vasconcelos, Thomas E Dever "}, {"type": "b", "children": [{"type": "t", "text": "An eIF2α-binding motif in protein phosphatase 1 subunit GADD34 and its viral orthologs is required to promote dephosphorylation of eIF2α."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1501557112"}], "href": "https://doi.org/10.1073/pnas.1501557112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26100893"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26100893"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "George Hodgson, Antonina Andreeva, Anne Bertolotti "}, {"type": "b", "children": [{"type": "t", "text": "Substrate recognition determinants of human eIF2α phosphatases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Open Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1098/rsob.210205"}], "href": "https://doi.org/10.1098/rsob.210205"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34847777"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34847777"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xiaoxing Wang, Ying Liao, Pei Ling Yap, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of protein kinase R activation and upregulation of GADD34 expression play a synergistic role in facilitating coronavirus replication by maintaining de novo protein synthesis in virus-infected cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.01546-09"}], "href": "https://doi.org/10.1128/JVI.01546-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19776135"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19776135"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Emily F A van 't Wout, Annemarie van Schadewijk, Ria van Boxtel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Pathog (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.ppat.1004946"}], "href": "https://doi.org/10.1371/journal.ppat.1004946"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26083346"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26083346"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Stephanie L Moon, Roy Parker "}, {"type": "b", "children": [{"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "EIF2B2"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " mutations in vanishing white matter disease hypersuppress translation and delay recovery during the integrated stress response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "RNA (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1261/rna.066563.118"}], "href": "https://doi.org/10.1261/rna.066563.118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29632131"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29632131"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yasuyuki Honjo, Takashi Ayaki, Takami Tomiyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased GADD34 in oligodendrocytes in Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2015.06.052"}], "href": "https://doi.org/10.1016/j.neulet.2015.06.052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26142647"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26142647"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Marianna Holczer, Gábor Bánhegyi, Orsolya Kapuy "}, {"type": "b", "children": [{"type": "t", "text": "GADD34 Keeps the mTOR Pathway Inactivated in Endoplasmic Reticulum Stress Related Autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0168359"}], "href": "https://doi.org/10.1371/journal.pone.0168359"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27992581"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27992581"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Peiying Song, Songpeng Yang, Hui Hua, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The regulatory protein GADD34 inhibits TRAIL-induced apoptosis via TRAF6/ERK-dependent stabilization of myeloid cell leukemia 1 in liver cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA118.006029"}], "href": "https://doi.org/10.1074/jbc.RA118.006029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30782845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30782845"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Seon Ae Roh, In Ja Park, Yong Sik Yoon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Feasibility of novel PPP1R15A and proposed ANXA11 single nucleotide polymorphisms as predictive markers for bevacizumab regimen in metastatic colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cancer Res Clin Oncol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00432-016-2177-5"}], "href": "https://doi.org/10.1007/s00432-016-2177-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27177629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27177629"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "E Morton, I M Macrae, C McCabe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the growth arrest and DNA damage protein GADD34 in the normal human heart and demonstration of alterations in expression following myocardial ischaemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cardiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ijcard.2005.01.051"}], "href": "https://doi.org/10.1016/j.ijcard.2005.01.051"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16337513"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16337513"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Hui Li, Wenqian Li, Shuangling Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enterovirus 71 Activates GADD34 via Precursor 3CD to Promote IRES-Mediated Viral Translation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Microbiol Spectr (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/spectrum.01388-21"}], "href": "https://doi.org/10.1128/spectrum.01388-21"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34985336"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34985336"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Matthew H Brush, Shirish Shenolikar "}, {"type": "b", "children": [{"type": "t", "text": "Control of cellular GADD34 levels by the 26S proteasome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00724-08"}], "href": "https://doi.org/10.1128/MCB.00724-08"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18794359"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18794359"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Wei Zhou, Matthew H Brush, Meng S Choy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association with endoplasmic reticulum promotes proteasomal degradation of GADD34 protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.212787"}], "href": "https://doi.org/10.1074/jbc.M110.212787"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21518769"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21518769"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Irene Chengjie Lee, Xue Yan Ho, Simi Elizabeth George, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oxidative stress promotes SIRT1 recruitment to the GADD34/PP1α complex to activate its deacetylase function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2017.152"}], "href": "https://doi.org/10.1038/cdd.2017.152"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28984870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28984870"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Vera Magg, Alessandro Manetto, Katja Kopp, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Turnover of PPP1R15A mRNA encoding GADD34 controls responsiveness and adaptation to cellular stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2024.114069"}], "href": "https://doi.org/10.1016/j.celrep.2024.114069"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38602876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38602876"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Chunyu Liu, Liang Chen, Yukun Cong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein phosphatase 1 regulatory subunit 15 A promotes translation initiation and induces G2M phase arrest during cuproptosis in cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-024-06489-w"}], "href": "https://doi.org/10.1038/s41419-024-06489-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38365764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38365764"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Y Song, S Liu, Z Zhao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Relationship between PPP1R15A gene polymorphism (rs611251) and Epstein-Barr virus-associated tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Virol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4149/av_2017_407"}], "href": "https://doi.org/10.4149/av_2017_407"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29186961"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29186961"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Danielle Hicks, Krithika Giresh, Lisa A Wrischnik, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The PPP1R15 Family of eIF2-alpha Phosphatase Targeting Subunits (GADD34 and CReP)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms242417321"}], "href": "https://doi.org/10.3390/ijms242417321"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38139150"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38139150"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Niangui Xu, Zhijie Xiao, Ting Zou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Induction of GADD34 Regulates the Neurotoxicity of Amyloid β."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Alzheimers Dis Other Demen (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/1533317514545616"}], "href": "https://doi.org/10.1177/1533317514545616"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25204313"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25204313"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "O H Minchenko, I V Kryvdiuk, O O Riabovol, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of IRE1 modifies the hypoxic regulation of GADD family gene expressions in U87 glioma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ukr Biochem J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15407/ubj88.02.025"}], "href": "https://doi.org/10.15407/ubj88.02.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29227599"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29227599"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Jose L Garrido, Seijii Maruo, Kenzo Takada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EBNA3C interacts with Gadd34 and counteracts the unfolded protein response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Virol J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1743-422X-6-231"}], "href": "https://doi.org/10.1186/1743-422X-6-231"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20040105"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20040105"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Ryosuke Watanabe, Yukihiro Tambe, Hirokazu Inoue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GADD34 inhibits mammalian target of rapamycin signaling via tuberous sclerosis complex and controls cell survival under bioenergetic stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2007)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17273797"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17273797"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Gennaro Gambardella, Leopoldo Staiano, Maria Nicoletta Moretti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GADD34 is a modulator of autophagy during starvation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Adv (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/sciadv.abb0205"}], "href": "https://doi.org/10.1126/sciadv.abb0205"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32978159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32978159"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Sachiko Ito, Yuriko Tanaka, Reina Oshino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GADD34 inhibits activation-induced apoptosis of macrophages through enhancement of autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep08327"}], "href": "https://doi.org/10.1038/srep08327"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25659802"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25659802"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Yong-Joon Jeon, Jin Hyun Kim, Jong-Il Shin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Salubrinal-Mediated Upregulation of eIF2α Phosphorylation Increases Doxorubicin Sensitivity in MCF-7/ADR Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cells (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14348/molcells.2016.2243"}], "href": "https://doi.org/10.14348/molcells.2016.2243"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26743901"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26743901"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Dawid Krokowski, Raul Jobava, Bo-Jhih Guan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Coordinated Regulation of the Neutral Amino Acid Transporter SNAT2 and the Protein Phosphatase Subunit GADD34 Promotes Adaptation to Increased Extracellular Osmolarity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.636217"}], "href": "https://doi.org/10.1074/jbc.M114.636217"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26041779"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26041779"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Daniel Y Wu, Douglas C Tkachuck, Rachel S Roberson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "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."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M200955200"}], "href": "https://doi.org/10.1074/jbc.M200955200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12016208"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12016208"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Wesley J Hung, Rachel S Roberson, Jaime Taft, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.10.3477-3486.2003"}], "href": "https://doi.org/10.1128/MCB.23.10.3477-3486.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12724406"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12724406"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "R Mukai, T Ohshima "}, {"type": "b", "children": [{"type": "t", "text": "HTLV-1 HBZ positively regulates the mTOR signaling pathway via inhibition of GADD34 activity in the cytoplasm."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2013.181"}], "href": "https://doi.org/10.1038/onc.2013.181"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23708656"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23708656"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Giovanna Clavarino, Souad Adriouach, Jean-Louis Quesada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Unfolded protein response gene GADD34 is overexpressed in rheumatoid arthritis and related to the presence of circulating anti-citrullinated protein antibodies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autoimmunity (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/08916934.2016.1138220"}], "href": "https://doi.org/10.3109/08916934.2016.1138220"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26829377"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26829377"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "F White, D McCaig, S M Brown, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of a growth arrest and DNA damage protein (GADD34) in the ischaemic human brain: implications for protein synthesis regulation and DNA repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropathol Appl Neurobiol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2990.2004.00584.x"}], "href": "https://doi.org/10.1111/j.1365-2990.2004.00584.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15541008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15541008"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Anna Powolny, Keiko Takahashi, Robin G Hopkins, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Induction of GADD gene expression by phenethylisothiocyanate in human colon adenocarcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.10733"}], "href": "https://doi.org/10.1002/jcb.10733"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14635187"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14635187"}]}]}]}