Biology:DNA damage-inducible transcript 3

From HandWiki
Short description: Human protein and coding gene


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

DNA damage-inducible transcript 3, also known as C/EBP homologous protein (CHOP), is a pro-apoptotic transcription factor that is encoded by the DDIT3 gene. [1][2] It is a member of the CCAAT/enhancer-binding protein (C/EBP) family of DNA-binding transcription factors. [2] The protein functions as a dominant-negative inhibitor by forming heterodimers with other C/EBP members, preventing their DNA binding activity. The protein is implicated in adipogenesis and erythropoiesis and has an important role in the cell's stress response. [2]

Structure

C/EBP proteins are known to have a conserved C-terminal structure, basic leucine zipper domain(bZIP), that is necessary for the formation of DNA-binding capable homodimers or heterodimers with other proteins or members of the C/EBP protein family. [3] CHOP is a relatively small (29kDa) protein that differs from most C/EBP proteins in several amino acid substitutions, which impacts its DNA-binding ability. [4]

CHOP protein structure created with PyMOL

Regulation and function

Due to a variety of upstream and downstream regulatory interactions, CHOP plays an important role in ER stress-induced apoptosis caused by a variety of stimuli such as pathogenic microbial or viral infections, amino acid starvation, mitochondrial stress, neurological diseases, and neoplastic diseases.

Under normal physiological conditions, CHOP is ubiquitously present at very low levels. [5] However, under overwhelming ER stress conditions, the expression of CHOP rises sharply along with the activation of apoptotic pathways in a wide variety of cells. [4] Those processes are mainly regulated by three factors: protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), and inositol requiring protein 1 (IRE1α) [6][7]

Upstream regulatory pathways

During ER stress, CHOP is mainly induced via activation of the integrated stress response pathways through the subsequent downstream phosphorylation of a translation initiation factor, eukaryotic initiation factor 2α (eIF2α), and induction of a transcription factor, activation transcription factor 4 (ATF4),[8] which converges on the promoters of target genes, including CHOP.

Integrated stress response, and thus CHOP expression, can be induced by

Under ER stress, activated transmembrane protein ATF6 translocates to the nucleus and interacts with ATF/cAMP response elements and ER stress-response elements,[13] binding the promoters and inducing transcription of several genes involved in unfolded protein response (including CHOP, XBP1 and others).[14][15] Thus, ATF6 activates the transcription of both CHOP and XBP-1, while XBP-1 can also upregulate the expression of CHOP.[16]

ER stress also stimulates transmembrane protein IRE1α activity.[17] Upon activation, IRE1α splices the XBP-1 mRNA introns to produce a mature and active XBP-1 protein,[18] that upregulates CHOP expression[19][20][21] IRE1α also stimulates the activation of the apoptotic-signaling kinase-1 (ASK1), which then activates the downstream kinases, Jun-N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK),[22] which participate in apoptosis induction along with CHOP.[23] The P38 MAP kinase family phosphorylates Ser78 and Ser81 of CHOP, which induces cell apoptosis.[24] Moreover, research studies found that the JNK inhibitors can suppress CHOP upregulation, indicating that JNK activation is also involved in the modulation of CHOP levels.[25]

Downstream pathways

Apoptosis induction via Mitochondria-Dependent Pathway

As a transcription factor, CHOP can regulate the expression of many anti-apoptotic and pro-apoptotic genes, including genes encoding the BCL2-family proteins, GADD34 and TRB-3.[26][27] In the CHOP-induced apoptotic pathway, CHOP regulates the expression of BCL2 protein family, that includes anti-apoptotic proteins (BCL2, BCL-XL, MCL-1, and BCL-W) and pro-apoptotic proteins (BAK, BAX, BOK, BIM, PUMA and others).[28][29]

Under ER stress, CHOP can function as either a transcriptional activator or repressor. It forms heterodimers with other C/EBP family transcription factors via bZIP-domain interactions to inhibit the expression of genes responsive to C/EBP family transcription factors, while enhancing the expression of other genes containing a specific 12–14 bp DNA cis-acting element.[30] CHOP can downregulate the expressions of anti-apoptotic BCL2 proteins, and upregulate the expression of proapoptotic proteins (BIM, BAK and BAX expression).[31][32] BAX-BAK oligomerization causes cytochrome c and apoptosis-inducing factor (AIF) release from mitochondria, eventually causing cell death.[33]

TRB3 pseudokinase is upregulated by the ER stress-inducible transcriptional factor, ATF4-CHOP.[34] CHOP interacts with TRB3, which contributes to the induction of apoptosis.[35][36][37] The expression of TRB3 has a pro-apoptotic capacity.[38][39] Therefore, CHOP also regulates apoptosis by upregulating the expression of the TRB3 gene.

Apoptosis induction via Death-Receptor Pathway

Death receptor-mediated apoptosis occurs via activation of death ligands (Fas, TNF, and TRAIL) and death receptors. Upon activation, the receptor protein, Fas-associated death domain protein, forms death-inducing signaling complex, which activates the downstream caspase cascade to induce apoptosis.[40]

A summary of CHOP upstream and downstream pathways

The PERK-ATF4-CHOP pathway can induce apoptosis by binding to the death receptors and upregulating the expression of death receptor 4 (DR4) and DR5. CHOP also interacts with the phosphorylated transcription factor JUN to form a complex that binds to the promoter region of DR4 in lung cancer cells.[40] The N-terminal domain of CHOP interacts with phosphorylated JUN to form a complex that regulates the expression of DR4 and DR5.[40] CHOP also upregulates the expression of DR5 by binding to the 5′-region of the DR5 gene.[41]

Under prolonged ER stress conditions, activation of the PERK-CHOP pathway will permit DR5 protein levels to rise, which accelerates the formation of the death-inducing signaling complex (DISC) and activates caspase-8,[42] leading to apoptosis[43]

Apoptosis induction through other downstream pathways

In addition, CHOP also mediates apoptosis through increasing the expression of the ERO1α (ER reductase)[6] gene, which catalyzes the production of H2O2 in the ER. The highly oxidized state of the ER results in H2O2 leakage into the cytoplasm, inducing the production of reactive oxygen species (ROS) and a series of apoptotic and inflammatory reactions.[6][44][45][46]

The overexpression of CHOP can lead to cell cycle arrest and result in cell apoptosis. At the same time, CHOP-induced apoptosis can also trigger cell death by inhibiting the expression of cell cycle regulatory protein, p21. The p21 protein inhibits the G1 phase of the cell cycle as well as regulates the activity of pre-apoptotic factors. Identified CHOP-p21 relationship may play a role in changing the cell state from adapting to ER stress towards pre-apoptotic activity.[47]

Under most conditions, CHOP can directly bind to the promoters of downstream related genes. However, under specific condition, CHOP can cooperate with other transcription factors to affect apoptosis. Recent studies have shown that Bcl-2-associated athanogene 5 (Bag5) is over-expressed in prostate cancer and inhibits ER stress-induced apoptosis. Overexpression of Bag5 results in decreased CHOP and BAX expression, and increased Bcl-2 gene expression.[48] Bag5 overexpression inhibited ER stress-induced apoptosis in the unfolded protein response by suppressing PERK-eIF2-ATF4 and enhancing the IRE1-Xbp1 activity.[49]

In general, the downstream targets of CHOP regulate the activation of apoptotic pathways, however, the molecular interaction mechanisms behind those processes remain to be discovered.

Interactions

DNA damage-inducible transcript 3 has been shown to interact with [proteins]:


Clinical significance

Role in fatty liver and hyperinsulinemia

File:CHOP mediates ER remodeling in beta cells.tif Chop gene deletion has been demonstrated protective against diet induced metabolic syndromes in mice.[56][57] Mice with germline Chop gene knockout have better glycemic control despite unchanged obesity. A plausible explanation for the observed dissociation between obesity and insulin resistance is that CHOP promotes insulin hypersecretion from pancreatic β cells.[58]

Furthermore, Chop depletion by a GLP1-ASO delievery system[59] was shown to have therapeutic effects of insulin reduction and fatty liver correction,[60] in preclinical mouse models.[58]

Role in microbial infection

CHOP-induced apoptosis pathways had been identified in cells infected by

Since CHOP has an important role of apoptosis induction during infection, it is an important target for further research that will help deepen the current understanding of pathogenesis and potentially provide an opportunity for invention of new therapeutic approaches. For example, small molecule inhibitors of CHOP expression may act as therapeutic options to prevent ER stress and microbial infections. Research had shown that small molecule inhibitors of PERK-eIF2α pathway limit PCV2 virus replication.[61]

Role in other diseases

The regulation of CHOP expression plays an important role in metabolic diseases and in some cancers through its function in mediating apoptosis. The regulation of CHOP expression could be a potential approach to affecting cancer cells through the induction of apoptosis.[47][25][40][70] In the intestinal epithelium, CHOP has been demonstrated to be downregulated under inflammatory conditions (in inflammatory bowel diseases and experimental models of colitis). In this context, CHOP seems to rather regulate the cell cycle than apoptotic processes.[71]

Mutations or fusions of CHOP (e.g. with FUS to form FUS-CHOP) can cause Myxoid liposarcoma.[45]

References

  1. ↑ "Induction by ionizing radiation of the gadd45 gene in cultured human cells: lack of mediation by protein kinase C". Molecular and Cellular Biology 11 (2): 1009–16. February 1991. doi:10.1128/MCB.11.2.1009. PMID 1990262. 
  2. ↑ 2.0 2.1 2.2 "Entrez Gene: DDIT3 DNA-damage-inducible transcript 3". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1649. 
  3. ↑ "Stress-induced binding of the transcriptional factor CHOP to a novel DNA control element". Molecular and Cellular Biology 16 (4): 1479–89. April 1996. doi:10.1128/MCB.16.4.1479. PMID 8657121. 
  4. ↑ 4.0 4.1 "A non-canonical pathway regulates ER stress signaling and blocks ER stress-induced apoptosis and heart failure". Nature Communications 8 (1): 133. July 2017. doi:10.1038/s41467-017-00171-w. PMID 28743963. Bibcode: 2017NatCo...8..133Y. 
  5. ↑ "CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription". Genes & Development 6 (3): 439–53. March 1992. doi:10.1101/gad.6.3.439. PMID 1547942. 
  6. ↑ 6.0 6.1 6.2 "Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis". The Journal of Cell Biology 186 (6): 783–92. September 2009. doi:10.1083/jcb.200904060. PMID 19752026. 
  7. ↑ "Roles of CHOP/GADD153 in endoplasmic reticulum stress". Cell Death and Differentiation 11 (4): 381–9. April 2004. doi:10.1038/sj.cdd.4401373. PMID 14685163. 
  8. ↑ "ER stress and diseases". The FEBS Journal 274 (3): 630–58. February 2007. doi:10.1111/j.1742-4658.2007.05639.x. PMID 17288551. 
  9. ↑ "GRP78 and CHOP modulate macrophage apoptosis and the development of bleomycin-induced pulmonary fibrosis". The Journal of Pathology 239 (4): 411–25. August 2016. doi:10.1002/path.4738. PMID 27135434. 
  10. ↑ "Endoplasmic reticulum stress implicated in chronic traumatic encephalopathy". Journal of Neurosurgery 124 (3): 687–702. March 2016. doi:10.3171/2015.3.JNS141802. PMID 26381255. 
  11. ↑ "Endoplasmic reticulum stress in the pathogenesis of fibrotic disease". The Journal of Clinical Investigation 128 (1): 64–73. January 2018. doi:10.1172/JCI93560. PMID 29293089. 
  12. ↑ "The Role of the PERK/eIF2α/ATF4/CHOP Signaling Pathway in Tumor Progression During Endoplasmic Reticulum Stress". Current Molecular Medicine 16 (6): 533–44. 2016. doi:10.2174/1566524016666160523143937. PMID 27211800. 
  13. ↑ "ER stress-induced cell death mechanisms". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1833 (12): 3460–3470. December 2013. doi:10.1016/j.bbamcr.2013.06.028. PMID 23850759. 
  14. ↑ "Antiapoptotic roles of ceramide-synthase-6-generated C16-ceramide via selective regulation of the ATF6/CHOP arm of ER-stress-response pathways". FASEB Journal 24 (1): 296–308. January 2010. doi:10.1096/fj.09-135087. PMID 19723703. 
  15. ↑ "Apelin-13 Alleviates Early Brain Injury after Subarachnoid Hemorrhage via Suppression of Endoplasmic Reticulum Stress-mediated Apoptosis and Blood-Brain Barrier Disruption: Possible Involvement of ATF6/CHOP Pathway". Neuroscience 388: 284–296. September 2018. doi:10.1016/j.neuroscience.2018.07.023. PMID 30036660. 
  16. ↑ "ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response". Molecular and Cellular Biology 20 (18): 6755–67. September 2000. doi:10.1128/mcb.20.18.6755-6767.2000. PMID 10958673. 
  17. ↑ "IRE1alpha kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates". Cell 138 (3): 562–75. August 2009. doi:10.1016/j.cell.2009.07.017. PMID 19665977. 
  18. ↑ "XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor". Cell 107 (7): 881–91. December 2001. doi:10.1016/s0092-8674(01)00611-0. PMID 11779464. 
  19. ↑ "The unfolded protein response: integrating stress signals through the stress sensor IRE1α". Physiological Reviews 91 (4): 1219–43. October 2011. doi:10.1152/physrev.00001.2011. PMID 22013210. 
  20. ↑ "Transcription Factor C/EBP Homologous Protein in Health and Diseases". Frontiers in Immunology 8: 1612. 2017. doi:10.3389/fimmu.2017.01612. PMID 29230213. 
  21. ↑ "Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities". Nature Reviews. Drug Discovery 7 (12): 1013–30. December 2008. doi:10.1038/nrd2755. PMID 19043451. 
  22. ↑ "Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP Kinase". Science 272 (5266): 1347–9. May 1996. doi:10.1126/science.272.5266.1347. PMID 8650547. Bibcode: 1996Sci...272.1347W. 
  23. ↑ "How IRE1 reacts to ER stress". Cell 132 (1): 24–6. January 2008. doi:10.1016/j.cell.2007.12.017. PMID 18191217. 
  24. ↑ "Attenuation of CHOP-mediated myocardial apoptosis in pressure-overloaded dominant negative p38α mitogen-activated protein kinase mice". Cellular Physiology and Biochemistry 27 (5): 487–96. 2011. doi:10.1159/000329970. PMID 21691066. 
  25. ↑ 25.0 25.1 "Tunicamycin enhances human colon cancer cells to TRAIL-induced apoptosis by JNK-CHOP-mediated DR5 upregulation and the inhibition of the EGFR pathway". Anti-Cancer Drugs 28 (1): 66–74. January 2017. doi:10.1097/CAD.0000000000000431. PMID 27603596. 
  26. ↑ "UPR induces transient burst of apoptosis in islets of early lactating rats through reduced AKT phosphorylation via ATF4/CHOP stimulation of TRB3 expression". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 300 (1): R92-100. January 2011. doi:10.1152/ajpregu.00169.2010. PMID 21068199. https://lirias.kuleuven.be/handle/123456789/486415. 
  27. ↑ "The transcription factor CHOP, a central component of the transcriptional regulatory network induced upon CCl4 intoxication in mouse liver, is not a critical mediator of hepatotoxicity". Archives of Toxicology 88 (6): 1267–80. June 2014. doi:10.1007/s00204-014-1240-8. PMID 24748426. 
  28. ↑ "CHOP potentially co-operates with FOXO3a in neuronal cells to regulate PUMA and BIM expression in response to ER stress". PLOS ONE 7 (6): e39586. 2012-06-28. doi:10.1371/journal.pone.0039586. PMID 22761832. Bibcode: 2012PLoSO...739586G. 
  29. ↑ "Neuronal apoptosis induced by endoplasmic reticulum stress is regulated by ATF4-CHOP-mediated induction of the Bcl-2 homology 3-only member PUMA". The Journal of Neuroscience 30 (50): 16938–48. December 2010. doi:10.1523/JNEUROSCI.1598-10.2010. PMID 21159964. 
  30. ↑ "Stress-induced binding of the transcriptional factor CHOP to a novel DNA control element". Molecular and Cellular Biology 16 (4): 1479–89. April 1996. doi:10.1128/mcb.16.4.1479. PMID 8657121. 
  31. ↑ "Cell death induced by endoplasmic reticulum stress". The FEBS Journal 283 (14): 2640–52. July 2016. doi:10.1111/febs.13598. PMID 26587781. 
  32. ↑ "The endoplasmic reticulum stress-C/EBP homologous protein pathway-mediated apoptosis in macrophages contributes to the instability of atherosclerotic plaques". Arteriosclerosis, Thrombosis, and Vascular Biology 30 (10): 1925–32. October 2010. doi:10.1161/ATVBAHA.110.206094. PMID 20651282. 
  33. ↑ "Interrogating the relevance of mitochondrial apoptosis for vertebrate development and postnatal tissue homeostasis". Genes & Development 30 (19): 2133–2151. October 2016. doi:10.1101/gad.289298.116. PMID 27798841. 
  34. ↑ "TRB3 is stimulated in diabetic kidneys, regulated by the ER stress marker CHOP, and is a suppressor of podocyte MCP-1". American Journal of Physiology. Renal Physiology 299 (5): F965-72. November 2010. doi:10.1152/ajprenal.00236.2010. PMID 20660016. 
  35. ↑ "Loss of C/EBP-β LIP drives cisplatin resistance in malignant pleural mesothelioma". Lung Cancer 120: 34–45. June 2018. doi:10.1016/j.lungcan.2018.03.022. PMID 29748013. 
  36. ↑ "HDAC4 protects cells from ER stress induced apoptosis through interaction with ATF4". Cellular Signalling 26 (3): 556–63. March 2014. doi:10.1016/j.cellsig.2013.11.026. PMID 24308964. 
  37. ↑ "TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death". The EMBO Journal 24 (6): 1243–55. March 2005. doi:10.1038/sj.emboj.7600596. PMID 15775988. 
  38. ↑ "TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver". Science 300 (5625): 1574–7. June 2003. doi:10.1126/science.1079817. PMID 12791994. Bibcode: 2003Sci...300.1574D. 
  39. ↑ "TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells". Oncology Letters 15 (1): 1343–1349. January 2018. doi:10.3892/ol.2017.7361. PMID 29391905. 
  40. ↑ 40.0 40.1 40.2 40.3 "DDIT3 and KAT2A Proteins Regulate TNFRSF10A and TNFRSF10B Expression in Endoplasmic Reticulum Stress-mediated Apoptosis in Human Lung Cancer Cells". The Journal of Biological Chemistry 290 (17): 11108–18. April 2015. doi:10.1074/jbc.M115.645333. PMID 25770212. 
  41. ↑ "Neddylation Inhibition Activates the Extrinsic Apoptosis Pathway through ATF4-CHOP-DR5 Axis in Human Esophageal Cancer Cells". Clinical Cancer Research 22 (16): 4145–57. August 2016. doi:10.1158/1078-0432.CCR-15-2254. PMID 26983464. https://aacr.figshare.com/articles/journal_contribution/Supplementary_Figure_from_Neddylation_Inhibition_Activates_the_Extrinsic_Apoptosis_Pathway_through_ATF4_CHOP_DR5_Axis_in_Human_Esophageal_Cancer_Cells/22455744/1/files/39906888.pdf. 
  42. ↑ "Opposing unfolded-protein-response signals converge on death receptor 5 to control apoptosis". Science 345 (6192): 98–101. July 2014. doi:10.1126/science.1254312. PMID 24994655. Bibcode: 2014Sci...345...98L. 
  43. ↑ "Apoptosis: a review of programmed cell death". Toxicologic Pathology 35 (4): 495–516. June 2007. doi:10.1080/01926230701320337. PMID 17562483. 
  44. ↑ "CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum". Genes & Development 18 (24): 3066–77. December 2004. doi:10.1101/gad.1250704. PMID 15601821. 
  45. ↑ 45.0 45.1 "Fusion of the EWS and CHOP genes in myxoid liposarcoma". Oncogene 12 (3): 489–94. February 1996. PMID 8637704. 
  46. ↑ "NADPH oxidase links endoplasmic reticulum stress, oxidative stress, and PKR activation to induce apoptosis". The Journal of Cell Biology 191 (6): 1113–25. December 2010. doi:10.1083/jcb.201006121. PMID 21135141. 
  47. ↑ 47.0 47.1 "Targeting unfolded protein response in cancer and diabetes". Endocrine-Related Cancer 22 (3): C1-4. June 2015. doi:10.1530/ERC-15-0106. PMID 25792543. 
  48. ↑ "GRP78 Interacting Partner Bag5 Responds to ER Stress and Protects Cardiomyocytes From ER Stress-Induced Apoptosis". Journal of Cellular Biochemistry 117 (8): 1813–21. August 2016. doi:10.1002/jcb.25481. PMID 26729625. 
  49. ↑ "Bcl-2 associated athanogene 5 (Bag5) is overexpressed in prostate cancer and inhibits ER-stress induced apoptosis". BMC Cancer 13: 96. March 2013. doi:10.1186/1471-2407-13-96. PMID 23448667. 
  50. ↑ "Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10". Molecular and Cellular Biology 16 (3): 1157–68. March 1996. doi:10.1128/MCB.16.3.1157. PMID 8622660. 
  51. ↑ 51.0 51.1 51.2 "CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins". Molecular and Cellular Biology 19 (11): 7589–99. November 1999. doi:10.1128/MCB.19.11.7589. PMID 10523647. 
  52. ↑ "C/EBP homologous protein (CHOP) up-regulates IL-6 transcription by trapping negative regulating NF-IL6 isoform". FEBS Letters 541 (1–3): 33–9. April 2003. doi:10.1016/s0014-5793(03)00283-7. PMID 12706815. 
  53. ↑ "Physical and functional association between GADD153 and CCAAT/enhancer-binding protein beta during cellular stress". The Journal of Biological Chemistry 271 (24): 14285–9. June 1996. doi:10.1074/jbc.271.24.14285. PMID 8662954. 
  54. ↑ "CHOP transcription factor phosphorylation by casein kinase 2 inhibits transcriptional activation". The Journal of Biological Chemistry 278 (42): 40514–20. October 2003. doi:10.1074/jbc.M306404200. PMID 12876286. 
  55. ↑ "Novel interaction between the transcription factor CHOP (GADD153) and the ribosomal protein FTE/S3a modulates erythropoiesis". The Journal of Biological Chemistry 275 (11): 7591–6. March 2000. doi:10.1074/jbc.275.11.7591. PMID 10713066. 
  56. ↑ Song, Benbo; Scheuner, Donalyn; Ron, David; Pennathur, Subramaniam; Kaufman, Randal J. (October 2008). "Chop deletion reduces oxidative stress, improves beta cell function, and promotes cell survival in multiple mouse models of diabetes". The Journal of Clinical Investigation 118 (10): 3378–3389. doi:10.1172/JCI34587. ISSN 0021-9738. PMID 18776938. 
  57. ↑ Maris, M.; Overbergh, L.; Gysemans, C.; Waget, A.; Cardozo, A. K.; Verdrengh, E.; Cunha, J. P. M.; Gotoh, T. et al. (April 2012). "Deletion of C/EBP homologous protein (Chop) in C57Bl/6 mice dissociates obesity from insulin resistance" (in en). Diabetologia 55 (4): 1167–1178. doi:10.1007/s00125-011-2427-7. ISSN 0012-186X. PMID 22237685. https://lirias.kuleuven.be/bitstream/123456789/340927/2/Maris%282012%29.pdf. 
  58. ↑ 58.0 58.1 Yong, Jing; Parekh, Vishal S.; Reilly, Shannon M.; Nayak, Jonamani; Chen, Zhouji; Lebeaupin, Cynthia; Jang, Insook; Zhang, Jiangwei et al. (2021-07-28). "Chop/Ddit3 depletion in β cells alleviates ER stress and corrects hepatic steatosis in mice". Science Translational Medicine 13 (604). doi:10.1126/scitranslmed.aba9796. ISSN 1946-6242. PMID 34321322. 
  59. ↑ Monia, Brett P.; Thazha P. Prakash & Garth A. Kinberger et al., "GLP-1 receptor ligand moiety conjugated oligonucleotides and uses thereof", WO patent application 2017192820, published 2017-11-09, assigned to Ionis Pharmaceuticals Inc.and AstraZeneca AB
  60. ↑ Yong, Jing; Johnson, James D.; Arvan, Peter; Han, Jaeseok; Kaufman, Randal J. (August 2021). "Therapeutic opportunities for pancreatic β-cell ER stress in diabetes mellitus". Nature Reviews. Endocrinology 17 (8): 455–467. doi:10.1038/s41574-021-00510-4. ISSN 1759-5037. PMID 34163039. 
  61. ↑ 61.0 61.1 "Porcine Circovirus 2 Deploys PERK Pathway and GRP78 for Its Enhanced Replication in PK-15 Cells". Viruses 8 (2): 56. February 2016. doi:10.3390/v8020056. PMID 26907328. 
  62. ↑ "HIV Tat-Mediated Induction of Human Brain Microvascular Endothelial Cell Apoptosis Involves Endoplasmic Reticulum Stress and Mitochondrial Dysfunction". Molecular Neurobiology 53 (1): 132–142. January 2016. doi:10.1007/s12035-014-8991-3. PMID 25409632. 
  63. ↑ "HIV-1 gp120 induces type-1 programmed cell death through ER stress employing IRE1α, JNK and AP-1 pathway". Scientific Reports 6: 18929. January 2016. doi:10.1038/srep18929. PMID 26740125. Bibcode: 2016NatSR...618929S. 
  64. ↑ "Upregulation of CHOP/GADD153 during coronavirus infectious bronchitis virus infection modulates apoptosis by restricting activation of the extracellular signal-regulated kinase pathway". Journal of Virology 87 (14): 8124–34. July 2013. doi:10.1128/JVI.00626-13. PMID 23678184. 
  65. ↑ "Endoplasmic reticulum stress pathway-mediated apoptosis in macrophages contributes to the survival of Mycobacterium tuberculosis". PLOS ONE 6 (12): e28531. 2011. doi:10.1371/journal.pone.0028531. PMID 22194844. Bibcode: 2011PLoSO...628531L. 
  66. ↑ "Induction of ER stress in macrophages of tuberculosis granulomas". PLOS ONE 5 (9): e12772. September 2010. doi:10.1371/journal.pone.0012772. PMID 20856677. Bibcode: 2010PLoSO...512772S. 
  67. ↑ "Endoplasmic reticulum stress contributes to Helicobacter pylori VacA-induced apoptosis". PLOS ONE 8 (12): e82322. 2013. doi:10.1371/journal.pone.0082322. PMID 24349255. Bibcode: 2013PLoSO...882322A. 
  68. ↑ "Shiga toxin 1 induces apoptosis through the endoplasmic reticulum stress response in human monocytic cells". Cellular Microbiology 10 (3): 770–80. March 2008. doi:10.1111/j.1462-5822.2007.01083.x. PMID 18005243. 
  69. ↑ "Shiga Toxins Induce Apoptosis and ER Stress in Human Retinal Pigment Epithelial Cells". Toxins 9 (10): 319. October 2017. doi:10.3390/toxins9100319. PMID 29027919. 
  70. ↑ "Different induction of GRP78 and CHOP as a predictor of sensitivity to proteasome inhibitors in thyroid cancer cells". Endocrinology 148 (7): 3258–70. July 2007. doi:10.1210/en.2006-1564. PMID 17431003. 
  71. ↑ "C/EBP homologous protein inhibits tissue repair in response to gut injury and is inversely regulated with chronic inflammation". Mucosal Immunology 7 (6): 1452–66. November 2014. doi:10.1038/mi.2014.34. PMID 24850428. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:DNA_damage-inducible_transcript_3&oldid=3613755"