Genomes and Genes
transcription factor chop
Summary: A CCAAT-enhancer binding protein that is induced by DNA DAMAGE and growth arrest. It serves as a dominant negative inhibitor of other CCAAT-enhancer binding proteins.
- Komatsu S, Miyazawa K, Moriya S, Takase A, Naito M, Inazu M, et al. Clarithromycin enhances bortezomib-induced cytotoxicity via endoplasmic reticulum stress-mediated CHOP (GADD153) induction and autophagy in breast cancer cells. Int J Oncol. 2012;40:1029-39 pubmed publisher..This combination further enhanced induction of the pro-apoptotic transcription factor CHOP (CADD153) and the chaperone protein GRP78...
- Fujiwara J, Sowa Y, Horinaka M, Koyama M, Wakada M, Miki T, et al. The anti-obesity drug orlistat promotes sensitivity to TRAIL by two different pathways in hormone-refractory prostate cancer cells. Int J Oncol. 2012;40:1483-91 pubmed publisher..We believe that the combination of orlistat and TRAIL in HRPC is promising as a new chemotherapeutic strategy. ..
- Soo K, Atkin J, Farg M, Walker A, Horne M, Nagley P. Bim links ER stress and apoptosis in cells expressing mutant SOD1 associated with amyotrophic lateral sclerosis. PLoS ONE. 2012;7:e35413 pubmed publisher..These sequential links between ER stress, CHOP upregulation, and Bim activation of mitochondrial apoptotic signalling indicate a clear pathway to cell death mediated by mutant SOD1. ..
- Ghosh A, Klocke B, Ballestas M, Roth K. CHOP potentially co-operates with FOXO3a in neuronal cells to regulate PUMA and BIM expression in response to ER stress. PLoS ONE. 2012;7:e39586 pubmed publisher..In summary, CHOP regulates the expression of multiple pro-apoptotic BH3-only molecules through multiple mechanisms, making CHOP an important therapeutic target relevant to a number of neurodegenerative conditions. ..
- Raciti M, Lotti L, Valia S, Pulcinelli F, di Renzo L. JNK2 is activated during ER stress and promotes cell survival. Cell Death Dis. 2012;3:e429 pubmed publisher..Our findings highlight a potential role for JNK2 in tumor cell survival, senescence and neurodegenerative diseases, in which ER stress, autophagy and lysosome activity are known to interplay. ..
- Han J, Murthy R, Wood B, Song B, Wang S, Sun B, et al. ER stress signalling through eIF2? and CHOP, but not IRE1?, attenuates adipogenesis in mice. Diabetologia. 2013;56:911-24 pubmed publisher..These results demonstrate that eIF2?-CHOP suppresses adipogenesis and limits expansion of fat mass in vivo in mice, rendering this pathway a potential therapeutic target. ..
- Han J, Back S, Hur J, Lin Y, Gildersleeve R, Shan J, et al. ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death. Nat Cell Biol. 2013;15:481-90 pubmed publisher..The findings suggest that limiting protein synthesis will be therapeutic for diseases caused by protein misfolding in the ER. ..
- Liao Y, Fung T, Huang M, Fang S, Zhong Y, Liu D. Upregulation of CHOP/GADD153 during coronavirus infectious bronchitis virus infection modulates apoptosis by restricting activation of the extracellular signal-regulated kinase pathway. J Virol. 2013;87:8124-34 pubmed publisher..This study provides solid evidence that induction of GADD153 by PERK and PKR plays an important regulatory role in the apoptotic process triggered by IBV infection. ..
- Saporta M, Shy B, Patzkó A, Bai Y, Pennuto M, Ferri C, et al. MpzR98C arrests Schwann cell development in a mouse model of early-onset Charcot-Marie-Tooth disease type 1B. Brain. 2012;135:2032-47 pubmed publisher..These mice provide a model by which we can begin to understand the early onset dysmyelination seen in patients with R98C and similar mutations. ..
- Xu L, Su L, Liu X. PKC? regulates death receptor 5 expression induced by PS-341 through ATF4-ATF3/CHOP axis in human lung cancer cells. Mol Cancer Ther. 2012;11:2174-82 pubmed publisher..Collectively, we show that PS-341 induces PKC?-dependent DR5 expression through activation of ERK/RSK2 and ER stress signaling pathway. ..
- Naranmandura H, Xu S, Koike S, Pan L, Chen B, Wang Y, et al. The endoplasmic reticulum is a target organelle for trivalent dimethylarsinic acid (DMAIII)-induced cytotoxicity. Toxicol Appl Pharmacol. 2012;260:241-9 pubmed publisher..In summary, our findings demonstrate that the endoplasmic reticulum is a target organelle for DMAIII-induced cytotoxicity. ..
- Lee J, Jung K, Morgan M, Kang Y, Lee H, Koo G, et al. Sensitization of TRAIL-induced cell death by 20(S)-ginsenoside Rg3 via CHOP-mediated DR5 upregulation in human hepatocellular carcinoma cells. Mol Cancer Ther. 2013;12:274-85 pubmed publisher..Taken together, our study identifies Rg3 as a novel anticancer therapeutic agent and supports the further development of Rg3 as a chemosensitizer in combined therapy with TRAIL. ..
- Alter J, Bengal E. Stress-induced C/EBP homology protein (CHOP) represses MyoD transcription to delay myoblast differentiation. PLoS ONE. 2011;6:e29498 pubmed publisher..This protein complex may reduce histone acetylation when bound to MyoD regulatory regions. Overall, our results suggest that the activation of a stress pathway in myoblasts transiently downregulate the myogenic program. ..
- Marwarha G, Dasari B, Ghribi O. Endoplasmic reticulum stress-induced CHOP activation mediates the down-regulation of leptin in human neuroblastoma SH-SY5Y cells treated with the oxysterol 27-hydroxycholesterol. Cell Signal. 2012;24:484-92 pubmed publisher..Furthermore, we demonstrate that the activation of the transcription factor CHOP in response to ER stress is pivotal in the attenuation of leptin expression as knocking-down CHOP ..
- Andersson M, Göransson M, Olofsson A, Andersson C, Aman P. Nuclear expression of FLT1 and its ligand PGF in FUS-DDIT3 carrying myxoid liposarcomas suggests the existence of an intracrine signaling loop. BMC Cancer. 2010;10:249 pubmed publisher..The findings of nuclear FLT1 protein and expression of corresponding ligands in MLS and normal tissues may have implications for tissue homeostasis and tumor development through auto- or intracrine signaling. ..
- Tabas I, Ron D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Biol. 2011;13:184-90 pubmed publisher..The molecular mechanisms linking ER stress to apoptosis are the topic of this review, with emphases on relevance to pathophysiology and integration and complementation among the various apoptotic pathways induced by ER stress. ..
- Moriya S, Miyazawa K, Kawaguchi T, Che X, Tomoda A. Involvement of endoplasmic reticulum stress-mediated CHOP (GADD153) induction in the cytotoxicity of 2-aminophenoxazine-3-one in cancer cells. Int J Oncol. 2011;39:981-8 pubmed publisher..TNM) and thapsigargin (TPG) indicated that although TNM and TPG potently induced pro-apoptotic transcription factor CHOP (GADD153) within 8 h of treatment, Phx-3 induced almost no CHOP within 48 h of treatment in U266 cells...
- Palam L, Baird T, Wek R. Phosphorylation of eIF2 facilitates ribosomal bypass of an inhibitory upstream ORF to enhance CHOP translation. J Biol Chem. 2011;286:10939-49 pubmed publisher..This new mechanism of translational control explains how expression of CHOP and the fate of cells are tightly linked to the levels of phosphorylated eIF2 and stress damage. ..
- Thorp E, Li G, Seimon T, Kuriakose G, Ron D, Tabas I. Reduced apoptosis and plaque necrosis in advanced atherosclerotic lesions of Apoe-/- and Ldlr-/- mice lacking CHOP. Cell Metab. 2009;9:474-81 pubmed publisher..These data provide direct evidence for a causal link between the ER stress effector CHOP and plaque necrosis and suggest that interventions weakening this arm of the UPR may lessen plaque progression. ..
- Wu X, Sun L, Zha W, Studer E, Gurley E, Chen L, et al. HIV protease inhibitors induce endoplasmic reticulum stress and disrupt barrier integrity in intestinal epithelial cells. Gastroenterology. 2010;138:197-209 pubmed publisher..HIV PIs induce ER stress and activate the unfolded protein response in intestinal epithelial cells, thus resulting in disruption of the epithelial barrier integrity. ..
- Yang W, Tiffany Castiglioni E, Koh H, Son I. Paraquat activates the IRE1/ASK1/JNK cascade associated with apoptosis in human neuroblastoma SH-SY5Y cells. Toxicol Lett. 2009;191:203-10 pubmed publisher..Therefore, current data indicate that paraquat activates the IRE1/ASK1/JNK cascade associated with apoptosis in SY5Y cells. ..
- Fradejas N, Pastor M, Burgos M, Beyaert R, Tranque P, Calvo S. Caspase-11 mediates ischemia-induced astrocyte death: involvement of endoplasmic reticulum stress and C/EBP homologous protein. J Neurosci Res. 2010;88:1094-105 pubmed publisher..In conclusion, our work contributes to clarifying the pathways leading to astrocyte death in response to ischemia by defining caspase-11 as a key mediator of the ER stress response acting downstream of CHOP. ..
- Rouschop K, van den Beucken T, Dubois L, Niessen H, Bussink J, Savelkouls K, et al. The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5. J Clin Invest. 2010;120:127-41 pubmed publisher..Our data therefore demonstrate that the UPR is an important mediator of the hypoxic tumor microenvironment and that it contributes to resistance to treatment through its ability to facilitate autophagy. ..
- Gorbatyuk M, Knox T, Lavail M, Gorbatyuk O, Noorwez S, Hauswirth W, et al. Restoration of visual function in P23H rhodopsin transgenic rats by gene delivery of BiP/Grp78. Proc Natl Acad Sci U S A. 2010;107:5961-6 pubmed publisher..Thus, the preservation of photoreceptor function resulting from elevated levels of BiP is due to suppression of apoptosis rather than to a promotion of rhodopsin folding. ..
- Martinon F, Chen X, Lee A, Glimcher L. TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages. Nat Immunol. 2010;11:411-8 pubmed publisher..Our findings identify an unsuspected critical function for XBP1 in mammalian host defenses. ..
- Halterman M, Gill M, Dejesus C, Ogihara M, Schor N, Federoff H. The endoplasmic reticulum stress response factor CHOP-10 protects against hypoxia-induced neuronal death. J Biol Chem. 2010;285:21329-40 pubmed publisher..Collectively, these findings indicate CHOP serves a more complex role in the neuronal response to hypoxic stress with involvement in both ischemic preconditioning and delayed neuroprotection. ..
- Tsukano H, Gotoh T, Endo M, Miyata K, Tazume H, Kadomatsu T, et al. The endoplasmic reticulum stress-C/EBP homologous protein pathway-mediated apoptosis in macrophages contributes to the instability of atherosclerotic plaques. Arterioscler Thromb Vasc Biol. 2010;30:1925-32 pubmed publisher..The ER stress-CHOP-Bax-mediated apoptosis in macrophages contributes to the instability of atherosclerotic plaques. ..
- Miyazaki Y, Kaikita K, Endo M, Horio E, Miura M, Tsujita K, et al. C/EBP homologous protein deficiency attenuates myocardial reperfusion injury by inhibiting myocardial apoptosis and inflammation. Arterioscler Thromb Vasc Biol. 2011;31:1124-32 pubmed publisher..The ER stress-induced, CHOP-mediated pathway, which is activated in part by superoxide overproduction after reperfusion, exacerbates myocardial ischemia/reperfusion injury by inducing cardiomyocyte apoptosis and myocardial inflammation. ..
- Bellodi C, Lidonnici M, Hamilton A, Helgason G, Soliera A, Ronchetti M, et al. Targeting autophagy potentiates tyrosine kinase inhibitor-induced cell death in Philadelphia chromosome-positive cells, including primary CML stem cells. J Clin Invest. 2009;119:1109-23 pubmed publisher..Together, these findings suggest that autophagy inhibitors may enhance the therapeutic effects of TKIs in the treatment of CML. ..
- Gow A, Wrabetz L. CHOP and the endoplasmic reticulum stress response in myelinating glia. Curr Opin Neurobiol. 2009;19:505-10 pubmed publisher..Together, these studies demonstrate that CHOP should be viewed more broadly as a cell-specific and context-specific mediator of adaptive or maladaptive responses to stress rather than a proapoptotic transcription factor. ..
- Pfaffenbach K, Gentile C, Nivala A, Wang D, Wei Y, Pagliassotti M. Linking endoplasmic reticulum stress to cell death in hepatocytes: roles of C/EBP homologous protein and chemical chaperones in palmitate-mediated cell death. Am J Physiol Endocrinol Metab. 2010;298:E1027-35 pubmed publisher..These data suggest that ER stress is linked to palmitate-mediated cell death via mechanisms that include JNK activation. ..
- Shao C, Lawrence M, Cobb M. Regulation of CCAAT/enhancer-binding protein homologous protein (CHOP) expression by interleukin-1 beta in pancreatic beta cells. J Biol Chem. 2010;285:19710-9 pubmed publisher..Knocking down CHOP by RNA interference protects beta cells from IL-1beta-induced apoptosis. These studies provide direct mechanistic links between cytokine-induced signaling pathways and CHOP-mediated apoptosis of beta cells. ..
- Liu G, Su L, Hao X, Zhong N, Zhong D, Singhal S, et al. Salermide up-regulates death receptor 5 expression through the ATF4-ATF3-CHOP axis and leads to apoptosis in human cancer cells. J Cell Mol Med. 2012;16:1618-28 pubmed publisher..This study highlights the importance of DR5 up-regulation in apoptosis induced by Sirt1/2 inhibition and elucidates the underlying mechanism in human NSCLC cells. ..
- Meares G, Mines M, Beurel E, Eom T, Song L, Zmijewska A, et al. Glycogen synthase kinase-3 regulates endoplasmic reticulum (ER) stress-induced CHOP expression in neuronal cells. Exp Cell Res. 2011;317:1621-8 pubmed publisher..Therefore, reduction of CHOP activation provides one mechanism by which inhibitors of GSK3 are capable of shifting cell fate towards survival instead of apoptosis following ER stress. ..
- Ng A, Chng W, Khan M. Curcumin sensitizes acute promyelocytic leukemia cells to unfolded protein response-induced apoptosis by blocking the loss of misfolded N-CoR protein. Mol Cancer Res. 2011;9:878-88 pubmed publisher..These findings identify the therapeutic potential of curcumin in APL and further establish the rationale of misfolded N-CoR protein as an attractive molecular target in APL. ..
- Pena J, Harris E. Dengue virus modulates the unfolded protein response in a time-dependent manner. J Biol Chem. 2011;286:14226-36 pubmed publisher..These results demonstrate that time-dependent activation of the unfolded protein response by DENV-2 can override inhibition of translation, prevent apoptosis, and prolong the viral life cycle. ..
- von dem Bussche A, Machida R, Li K, Loevinsohn G, Khander A, Wang J, et al. Hepatitis C virus NS2 protein triggers endoplasmic reticulum stress and suppresses its own viral replication. J Hepatol. 2010;53:797-804 pubmed publisher..Abrogation of HCV infection/replication, by an inhibitor of the NS3 protease, relieved ER stress. HCV infection can induce ER stress, with NS2 protein being a major mediator. The stress can be relieved by a feedback mechanism. ..
- Li G, Mongillo M, Chin K, Harding H, Ron D, Marks A, et al. Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis. J Cell Biol. 2009;186:783-92 pubmed publisher..Macrophages from insulin-resistant ob/ob mice, another model of ER stress, also have elevated IICR. These data shed new light on how the CHOP pathway of apoptosis triggers calcium-dependent apoptosis through an ERO1-alpha-IP3R pathway. ..
- Ishikawa F, Akimoto T, Yamamoto H, Araki Y, Yoshie T, Mori K, et al. Gene expression profiling identifies a role for CHOP during inhibition of the mitochondrial respiratory chain. J Biochem. 2009;146:123-32 pubmed publisher..This study demonstrated the importance of CHOP-10 in coordinating individual gene expression in response to the mitochondrial stress. ..
- Galehdar Z, Swan P, Fuerth B, Callaghan S, Park D, Cregan S. Neuronal apoptosis induced by endoplasmic reticulum stress is regulated by ATF4-CHOP-mediated induction of the Bcl-2 homology 3-only member PUMA. J Neurosci. 2010;30:16938-48 pubmed publisher..Rather, we found that ATF4 induces expression of the transcription factor CHOP (C/EBP homologous protein) and that CHOP in turn activates PUMA induction...
- Pino S, O Sullivan Murphy B, Lidstone E, Yang C, Lipson K, Jurczyk A, et al. CHOP mediates endoplasmic reticulum stress-induced apoptosis in Gimap5-deficient T cells. PLoS ONE. 2009;4:e5468 pubmed publisher..These findings indicate a direct relationship between Gimap5 and the maintenance of ER homeostasis in the survival of T cells. ..
- Nakayama Y, Endo M, Tsukano H, Mori M, Oike Y, Gotoh T. Molecular mechanisms of the LPS-induced non-apoptotic ER stress-CHOP pathway. J Biochem. 2010;147:471-83 pubmed publisher..We concluded that apoptosis is prevented in LPS-treated macrophages, because the ER function-protective mechanisms are induced before CHOP expression, and induction level of CHOP is low. ..
- Bento C, Andersson M, Aman P. DDIT3/CHOP and the sarcoma fusion oncoprotein FUS-DDIT3/TLS-CHOP bind cyclin-dependent kinase 2. BMC Cell Biol. 2009;10:89 pubmed publisher..We conclude that DDIT3 binds CDK2 and that many of the observed biological effects of DDIT3 may involve interaction with CDK2. ..
- Srinivasan K, Sharma S. Sodium phenylbutyrate ameliorates focal cerebral ischemic/reperfusion injury associated with comorbid type 2 diabetes by reducing endoplasmic reticulum stress and DNA fragmentation. Behav Brain Res. 2011;225:110-6 pubmed publisher..It also suggest that targeting ER stress might offer a promising therapeutic approach and benefits against ischemic stroke associated with comorbid type 2 diabetes. ..
- Zhang Y, Yang X, Shi H, Dong L, Bai J. Effect of ?-linolenic acid on endoplasmic reticulum stress-mediated apoptosis of palmitic acid lipotoxicity in primary rat hepatocytes. Lipids Health Dis. 2011;10:122 pubmed publisher..Linolenic acid may provide a useful strategy to avoid the lipotoxicity of dietary palmitic acid and nutrient overload accompanied with obesity and NAFLD. ..
- Seimon T, Kim M, Blumenthal A, Koo J, Ehrt S, Wainwright H, et al. Induction of ER stress in macrophages of tuberculosis granulomas. PLoS ONE. 2010;5:e12772 pubmed publisher..Therefore future work is needed to determine if ER-stress is causative for apoptosis and plays a role in the host response to infection. ..
- Hung J, Hsu Y, Ni W, Tsai Y, Yang C, Kuo P, et al. Oxidative and endoplasmic reticulum stress signaling are involved in dehydrocostuslactone-mediated apoptosis in human non-small cell lung cancer cells. Lung Cancer. 2010;68:355-65 pubmed publisher..This study demonstrates that DHE may be a novel anticancer agent for the treatment of non-small cell lung cancer. ..
- Chigurupati S, Wei Z, Belal C, Vandermey M, Kyriazis G, Arumugam T, et al. The homocysteine-inducible endoplasmic reticulum stress protein counteracts calcium store depletion and induction of CCAAT enhancer-binding protein homologous protein in a neurotoxin model of Parkinson disease. J Biol Chem. 2009;284:18323-33 pubmed publisher