Affinage

Showing DDIT3 — CHOP is a alias.

DDIT3

DDIT3 upstream open reading frame protein · UniProt P0DPQ6

Length
34 aa
Mass
4.3 kDa
Annotated
2026-06-09
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DDIT3 (CHOP/GADD153) is a stress-inducible bZIP transcription factor whose expression is driven primarily by ER stress rather than by DNA damage or growth arrest per se (PMID:8754828), and which executes cell-fate decisions during the stress response chiefly by dimerizing with C/EBP family members and redirecting them away from classical C/EBP sites to non-classical targets (PMID:8125258, PMID:7588595). Through heterodimerization with C/EBPα and C/EBPβ, DDIT3 suppresses C/EBP-dependent transcription and blocks adipogenic and osteoblastic differentiation (PMID:7588595, PMID:16880521), and it forms autoregulatory and inhibitory heterodimers with C/EBPβ and ATF3 that limit its own induction and disable partner DNA binding (PMID:8662954, PMID:8622660). Functionally DDIT3 imposes G1/S cell cycle arrest, an activity requiring its leucine zipper and basic region (PMID:8125258), and drives apoptosis through a domain-separable program that downregulates Bcl-2 (PMID:8898082) and, via cooperation with phospho-c-Jun/AP-1, induces the proapoptotic gene PUMA (PMID:20430872); it further amplifies death signaling through PERK-dependent induction of miR-216b, which targets c-Jun (PMID:27173017). DDIT3 activity is tuned post-translationally: p38 MAP kinase phosphorylates Ser78/Ser81 to enhance its transcriptional and differentiation-inhibitory activity (PMID:8650547), it is targeted for proteasomal degradation by the SPOP-CUL3-RBX1 E3 ligase via a degron in its transactivation domain (PMID:24990631), and it is stabilized by TXNIP binding that reduces its ubiquitination (PMID:37153733). Beyond classical transcriptional repression, DDIT3 partitions between cytoplasmic and nuclear pools with distinct target genes and phenotypes (PMID:22496745), serves as an attenuator (rheostat) of the mitochondrial integrated stress response by interacting with C/EBPβ to constrain ATF4 (PMID:34039602), and directs metabolic reprogramming during glutamine deprivation through nuclear suppression of TIGAR and a mitochondrial pool acting via LONP1 to suppress OXPHOS components (PMID:34105294). In vivo, DDIT3 is a required effector of ER-stress-driven cell death in pseudoachondroplasia chondrocytes (PMID:22154935), photoreceptor degeneration (PMID:33691741), and TXNIP-dependent mitochondrial ROS/NLRP3/ASK1 injury in nephrotic syndrome (PMID:35994650), and it suppresses innate antiviral immunity through a DDIT3-OTUD1-Smurf1-MAVS degradation axis (PMID:33361422). Chromosomal translocations fuse DDIT3 to FUS or EWS to generate myxoid liposarcoma oncoproteins that sequester CEBPB from chromatin and BAF-remodeled adipogenic enhancers and activate IGF2/IGF-IR signaling (PMID:8510758, PMID:35390276, PMID:28637688).

Mechanistic history

Synthesis pass · year-by-year structured walk · 34 steps
  1. 1993 High

    Established the disease relevance of DDIT3 by showing it is the recurrent fusion partner in myxoid liposarcoma, defining a chimeric oncoprotein in which the FUS RNA-binding domain is replaced by the DDIT3 DNA-binding/leucine-zipper module.

    Evidence Molecular cloning of the t(12;16) translocation product and cDNA characterization

    PMID:8510758

    Open questions at the time
    • Did not define the transcriptional or chromatin mechanism of the fusion
    • No functional comparison to wild-type DDIT3
  2. 1994 High

    Defined a core cellular function by showing DDIT3 imposes G1/S arrest dependent on its dimerization and basic domains, and that the oncogenic fusion lacks this activity and dominantly interferes with it.

    Evidence Microinjection of plasmid and bacterial protein into synchronized NIH-3T3 cells with BrdU readout and domain mutagenesis

    PMID:8125258

    Open questions at the time
    • Direct cell-cycle target genes not identified
    • Non-classical DNA sites not mapped
  3. 1995 High

    Resolved the mechanism of differentiation block by showing DDIT3 heterodimerizes with C/EBPα/β, redirects them off classical sites, and acts upstream by suppressing C/EBPα accumulation.

    Evidence Ectopic expression in 3T3-L1 adipocytes with C/EBPα rescue and expression analysis

    PMID:7588595

    Open questions at the time
    • Did not define the non-classical site sequences
    • Mechanism of C/EBPα suppression at gene level unresolved
  4. 1996 High

    Identified the upstream activating stimulus and post-translational control, establishing that DDIT3 induction is driven by ER stress and that p38 phosphorylation of Ser78/81 enhances its activity.

    Evidence Temperature-sensitive glycosylation mutants and BiP overexpression for induction; in vitro p38 kinase assay, SB203580, and serine mutagenesis for phosphorylation

    PMID:8650547 PMID:8754828

    Open questions at the time
    • Upstream ER-stress sensor pathway not connected at this stage
    • How phosphorylation alters dimer partner choice unresolved
  5. 1996 High

    Established DDIT3 as a proapoptotic factor with a domain-separable, p53-independent program linked to Bcl-2 downregulation, and as an inhibitor of C/EBP-dependent survival signals.

    Evidence Conditional expression in M1 and 32D myeloid cells, domain mutagenesis, Bcl-2 rescue, and trans-activation/apoptosis assays

    PMID:8764117 PMID:8898082

    Open questions at the time
    • Direct transcriptional link to Bcl-2 not established
    • Apoptotic effectors downstream not defined
  6. 1996 High

    Defined dimerization-based inhibitory mechanisms by showing DDIT3 forms non-functional heterodimers with C/EBPβ (autoregulatory feedback) and with ATF3, abolishing partner DNA binding.

    Evidence Endogenous co-IP, EMSA, and reporter assays in arsenite-treated PC12 cells; heterodimerization and DNA-binding assays for ATF3

    PMID:8622660 PMID:8662954

    Open questions at the time
    • In vivo relevance of each heterodimer not quantified
    • Partner selectivity rules not defined
  7. 1997 High

    Placed DDIT3 in a mutual negative regulatory loop with ATF3, which represses the DDIT3 promoter via AP-1 and C/EBP-ATF composite sites.

    Evidence Promoter mapping by EMSA, in vitro transcription, ATF3 overexpression, and a CCl4 in vivo model

    PMID:9343434

    Open questions at the time
    • Physiological contexts where the loop dominates not defined
  8. 1999 High

    Extended DDIT3 beyond C/EBP biology by identifying a non-bZIP partner (ribosomal protein FTE/S3a) and demonstrating functional rescue of erythroid differentiation.

    Evidence Reciprocal co-IP (bacterial and endogenous), co-localization, and differentiation rescue in erythroleukemia cells

    PMID:10713066

    Open questions at the time
    • Functional significance of the cytosolic interaction unclear
    • Whether interaction affects transcription unresolved
  9. 1999 Medium

    Characterized a cis-acting control on DDIT3 mRNA stability through an AU-rich element in a 3'UTR region overlapping the MetRS gene.

    Evidence Gene-overlap mapping and luciferase reporter assays with 3'UTR deletion constructs in NIH-3T3 cells

    PMID:10448063

    Open questions at the time
    • Trans-acting factors binding the ARE not identified
    • Endogenous transcript stability not directly measured
  10. 2001 High

    Identified transcriptional repression of DDIT3 by NF-κB p65 as a cytoprotective brake against ER-stress apoptosis.

    Evidence GADD153 promoter reporters, p65-/- MEFs, and parthenolide treatment with viability assays

    PMID:11360202

    Open questions at the time
    • Mechanism of p65 promoter repression not defined
    • p50 vs p65 specificity basis unresolved
  11. 2000 High

    Broadened DDIT3 signaling reach by showing it binds TCF factors to inhibit Wnt/TCF transcription, an activity requiring the N-terminal transactivation domain rather than the dimerization domain.

    Evidence TCF-binding and reporter assays plus Xenopus axis-induction epistasis with domain deletion mutants

    PMID:16434966

    Open questions at the time
    • Mammalian developmental relevance not tested
    • Direct TCF target genes affected not defined
  12. 2004 Medium

    Mapped additional regulators of DDIT3 expression: TRAF7-MEKK3 signaling activates DDIT3, while ETS1/FLI-1 transactivate the promoter via an ETS binding site.

    Evidence Co-IP/antisense and reporter assays for TRAF7-MEKK3; promoter-reporter and EMSA for ETS1/FLI-1

    PMID:10510472 PMID:15001576

    Open questions at the time
    • Endogenous DDIT3 induction by ETS factors not validated
    • Physiological stimuli engaging TRAF7-MEKK3-DDIT3 unclear
  13. 2005 High

    Revealed how the fusion oncoprotein diverges from wild-type DDIT3, with FUS-DDIT3 driving CEBPB-dependent IL-6 induction and opposite effects on IL-8.

    Evidence Isogenic DDIT3-GFP and FUS-DDIT3-GFP transfectants with microarray, CEBPB siRNA epistasis, and ChIP at the IL-6 promoter

    PMID:15688424

    Open questions at the time
    • How fusion redirects CEBPB to target promoters not yet mechanistically defined here
  14. 2006 High

    Established DDIT3 control of osteoblast differentiation via C/EBPβ inhibition, with context-dependent outcomes across cell systems.

    Evidence Overexpression and CHOP-KO osteoblast differentiation assays, heterodimerization and Runx2/DNA-binding inhibition, and EMSA/supershift in ST-2 cells

    PMID:14684614 PMID:16880521

    Open questions at the time
    • Opposing differentiation outcomes between systems not reconciled
    • Role of BMP-2/Smad enhancement vs C/EBP inhibition unresolved
  15. 2008 Medium

    Expanded DDIT3 dimer repertoire by showing JDP2 association redirects it to TRE elements and counteracts its proapoptotic activity.

    Evidence Co-IP, in vitro/in vivo DNA binding, reporter assays, and ER-stress viability assays

    PMID:18463134

    Open questions at the time
    • Endogenous JDP2-DDIT3 target genes not identified
    • Physiological balance of pro- vs anti-apoptotic dimers unclear
  16. 2009 Medium

    Linked DDIT3 and FUS-DDIT3 to cell-cycle machinery through CDK2 binding and altered cytoskeletal-protein affinity.

    Evidence Co-IP interaction screen among G1 cyclins/CDKs

    PMID:20017906

    Open questions at the time
    • Single Co-IP screen with limited functional follow-up
    • Whether CDK2 binding mediates G1 arrest not tested
  17. 2011 High

    Established DDIT3 as a direct regulator of microRNAs, inducing miR-708 (within Odz4) during ER stress to suppress rhodopsin.

    Evidence Genome-wide miRNA profiling with miR-708 gain/loss-of-function and rhodopsin target validation

    PMID:21402790

    Open questions at the time
    • Direct DDIT3 binding at the miR-708 locus not mapped
    • Broader miR-708 target network unresolved
  18. 2011 High

    Demonstrated that DDIT3 is a required effector of mutant-protein ER retention and chondrocyte death in pseudoachondroplasia.

    Evidence Genetic epistasis crossing D469del-COMP transgenic mice onto a Ddit3-null background

    PMID:22154935

    Open questions at the time
    • Mechanism linking DDIT3 to mutant COMP retention not defined
    • Transcriptional targets mediating chondrocyte death unidentified
  19. 2012 High

    Established that DDIT3 has compartment-specific functions, with cytoplasmic and nuclear pools regulating largely non-overlapping gene sets and distinct phenotypes (migration vs G1 arrest).

    Evidence Tamoxifen-inducible localization-targeted constructs with genome-wide expression, migration, and cell-cycle assays

    PMID:22496745

    Open questions at the time
    • Partner identities in each compartment not defined
    • How localization is regulated unresolved
  20. 2012 High

    Revealed post-transcriptional control of DDIT3 during adipogenesis, with RNase L destabilizing CHOP10 mRNA to permit terminal differentiation.

    Evidence RNase L-KO MEFs, mRNA association, ectopic RNase L rescue, siRNA epistasis, and aged-KO mouse phenotyping

    PMID:22441668

    Open questions at the time
    • Direct RNase L cleavage site on CHOP10 mRNA not mapped
  21. 2014 High

    Defined the principal degradation pathway for DDIT3, identifying it as a SPOP-CUL3-RBX1 substrate via a Ser/Thr-rich degron, with disease-mutant SPOP defective in its turnover.

    Evidence Ubiquitination assays, proteasome inhibition, degron mapping, and prostate-cancer SPOP mutant analysis

    PMID:24990631

    Open questions at the time
    • Signals regulating SPOP recognition of DDIT3 not defined
    • Cell contexts where this turnover dominates unclear
  22. 2016 High

    Connected DDIT3 to apoptotic amplification by showing PERK-dependent CHOP induces miR-216b to silence c-Jun and sensitize cells to ER-stress death.

    Evidence Loss-of-function at PERK, CHOP, and IRE1 nodes with miR-216b gain/loss and c-Jun target validation

    PMID:27173017

    Open questions at the time
    • Direct DDIT3 binding at the miR-216b promoter not mapped
  23. 2010 High

    Defined a transcription-factor cooperation mechanism in which DDIT3 partners phospho-c-Jun at the PUMA AP-1 site to drive lipotoxic apoptosis.

    Evidence Co-IP, ChIP at the PUMA AP-1 site, and CHOP shRNA with PUMA/Bax readouts in hepatocyte-relevant models

    PMID:20430872

    Open questions at the time
    • No functional DDIT3 binding site in the PUMA promoter found; reliance on AP-1 cooperation only
  24. 2017 High

    Distinguished DDIT3-dependent death pathways in vivo, showing DDIT3 and JUN act independently and additively in retinal ganglion cell soma but neither prevents axonal degeneration.

    Evidence Single and double Jun/Ddit3 knockout mice in optic nerve crush with survival and electrophysiology readouts

    PMID:28969695

    Open questions at the time
    • Independent DDIT3 effector genes in RGCs not defined
    • Why axonal degeneration is unaffected unresolved
  25. 2017 Medium

    Mapped an oncogenic signaling output of the fusion protein, with FUS-DDIT3 inducing IGF2 to activate IGF-IR/PI3K/Akt in myxoid liposarcoma.

    Evidence FUS-DDIT3 overexpression/RNAi with IGF2 and pathway readouts and IGF-IR inhibition in vitro and in a CAM model

    PMID:28637688

    Open questions at the time
    • Direct vs indirect IGF2 transcriptional control not resolved
    • Single-lab validation
  26. 2019 High

    Placed DDIT3 downstream of HMOX1-induced ER stress as a required effector of photoreceptor degeneration.

    Evidence AAV-HMOX1 overexpression in Ddit3-KO mice with RNA-seq, TUNEL, ERG, and immunostaining

    PMID:33691741

    Open questions at the time
    • DDIT3 death-effector targets in photoreceptors not identified
  27. 2021 High

    Reframed DDIT3 in the mitochondrial ISR as an attenuator rather than activator, interacting with C/EBPβ to constrain ATF4 and prevent chronic ISR-driven energy crisis.

    Evidence Transgenic mitochondrial cardiomyopathy mice with CHOP-C/EBPβ interaction studies, ATF4/translation profiling, and cardiac/metabolic readouts

    PMID:34039602

    Open questions at the time
    • Molecular basis of how the heterodimer limits ATF4 not fully defined
    • Generality beyond mitochondrial stress unclear
  28. 2021 Medium

    Established DDIT3 as a dual-compartment metabolic regulator during glutamine deprivation, suppressing TIGAR in the nucleus to drive glycolysis and acting via a mitochondrial pool/LONP1 to suppress OXPHOS and ROS.

    Evidence Glutamine-deprivation induction, subcellular fractionation, LONP1 interaction, COQ9/COX4 regulation, and metabolic flux analysis

    PMID:34105294

    Open questions at the time
    • Mechanism of DDIT3 mitochondrial import not defined
    • Direct vs indirect TIGAR regulation unresolved
  29. 2021 Medium

    Extended DDIT3 to innate immunity, defining a DDIT3-OTUD1-Smurf1-MAVS axis that degrades MAVS and suppresses type I interferon.

    Evidence Overexpression/knockdown, NF-κB analysis, deubiquitination and ubiquitination assays, and Ddit3-KO mice with viral infection

    PMID:33361422

    Open questions at the time
    • Primarily bovine MDBK cells with partial mouse validation
    • Direct transcriptional control of OTUD1 not fully mapped
  30. 2021 High

    Defined a physiological β-cell role for DDIT3 in ER Ca2+ buffering and insulin secretion, with therapeutic targeting by a GLP1-conjugated antisense oligonucleotide.

    Evidence β-cell-specific Chop-KO mice on HFD with islet Ca2+ flux, chaperone profiling, hepatic lipid measurement, and GLP1-ASO treatment

    PMID:34321322

    Open questions at the time
    • Transcriptional targets governing ER chaperone remodeling not defined
  31. 2021 High

    Identified a direct transcriptional output linking DDIT3 to autophagy via SIRT1 promoter binding and the SIRT1-AKT pathway in chondrocytes.

    Evidence ChIP for SIRT1 promoter binding, overexpression/knockdown, Ddit3-KO mice, and autophagic-flux/SIRT1-modulator epistasis

    PMID:34087318

    Open questions at the time
    • Dimer partner at the SIRT1 promoter not identified
  32. 2022 High

    Resolved the chromatin mechanism of the fusion oncoprotein, showing FUS-DDIT3 sequesters CEBPB and inhibits BAF complex remodeling at adipogenic enhancers, mimicking SMARCB1-deficient tumors.

    Evidence Co-IP, ChIP-seq, ATAC-seq, transcriptomics, BAF ATPase inhibition, and FUS-DDIT3 knockdown

    PMID:35390276

    Open questions at the time
    • Whether wild-type DDIT3 similarly affects BAF not tested
  33. 2022 High

    Connected DDIT3 to TXNIP-driven mitochondrial injury, showing DDIT3 upregulation promotes TXNIP mitochondrial shuttling to drive ROS, NLRP3 inflammasome, and ASK1-dependent apoptosis in nephrotic syndrome.

    Evidence Chop-/- and Txnip-/- mice, TXNIP subcellular fractionation, mitochondrial ROS imaging, and NLRP3/ASK1 assays

    PMID:35994650

    Open questions at the time
    • How DDIT3 promotes TXNIP translocation mechanistically unresolved
  34. 2023 High

    Defined a stabilizing post-translational control by TXNIP, which binds the DDIT3 α-helix to reduce its ubiquitination and elevate protein levels in NASH.

    Evidence Co-IP domain mapping, ubiquitination assays, and Txnip knockdown in NASH mouse livers

    PMID:37153733

    Open questions at the time
    • Relationship between TXNIP stabilization and SPOP-mediated turnover not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DDIT3 selects among its many dimer partners and subcellular pools to choose between cytoprotective attenuation, differentiation block, and apoptosis in a given stress context remains unresolved.
  • No unifying model of partner/compartment selection
  • Genome-wide direct DDIT3 binding landscape across stresses incomplete
  • Quantitative interplay of p38 phosphorylation, SPOP degradation, and TXNIP stabilization in setting DDIT3 levels undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-8953897 Cellular responses to stimuli 5 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-1430728 Metabolism 1 R-HSA-168256 Immune System 1
Partners
ATF3CDK2CEBPACEBPBJDP2JUNSPOPTXNIP
Complex memberships
EWS-DDIT3 fusion oncoproteinFUS-DDIT3 fusion oncoprotein

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 CHOP (DDIT3) is fused to TLS (FUS), a novel nuclear RNA-binding protein, in human myxoid liposarcoma via t(12;16)(q13;p11) translocation; in the TLS-CHOP fusion protein, the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP, creating a chimeric oncoprotein. Molecular cloning of translocation-associated gene product, cDNA cloning, CHOP-specific antibody/probe characterization Nature High 8510758
1994 CHOP (DDIT3) induces G1/S cell cycle arrest; microinjection of CHOP expression plasmids or bacterially-expressed CHOP protein into NIH-3T3 cells blocked progression from G1 to S phase. This effect requires the leucine zipper dimerization domain and the basic region of CHOP. The oncogenic fusion TLS-CHOP fails to cause G1 arrest and interferes with wild-type CHOP-induced arrest. CHOP-C/EBP heterodimers are directed away from classical C/EBP binding sites to unique 'non-classical' sites. Microinjection of expression plasmids and bacterially-expressed protein into synchronized NIH-3T3 cells; BrdU incorporation assay; site-directed mutagenesis of CHOP domains Genes & development High 8125258
1995 CHOP (DDIT3) inhibits adipogenesis in 3T3-L1 cells by forming heterodimers with C/EBP alpha and beta, directing the complex away from classical C/EBP binding sites, and suppressing C/EBP alpha and beta gene expression. Ectopic C/EBP alpha expression bypasses CHOP inhibition, indicating CHOP acts upstream by inhibiting C/EBP alpha accumulation rather than only blocking DNA binding. Ectopic expression of CHOP in 3T3-L1 cells; C/EBP alpha rescue experiment; gene expression analysis The EMBO journal High 7588595
1996 CHOP (DDIT3) is phosphorylated on serine residues 78 and 81 by p38 MAP kinase in vitro; a specific p38 inhibitor (SB203580) abolishes stress-inducible in vivo phosphorylation of CHOP. Phosphorylation on these residues enhances CHOP transcriptional activation activity and is required for CHOP's full inhibitory effect on adipose cell differentiation. In vitro kinase assay with p38; pharmacological inhibitor SB203580 in vivo; site-directed mutagenesis of serine residues; transcriptional activation and differentiation assays Science (New York, N.Y.) High 8650547
1996 CHOP (GADD153/DDIT3) gene induction is primarily driven by ER stress rather than DNA damage or growth arrest per se. Cells with conditional defects in protein glycosylation induce CHOP at non-permissive temperature; overexpression of ER chaperone BiP/GRP78 attenuates CHOP induction by ER stressors and, unexpectedly, also attenuates induction by methylmethane sulfonate, suggesting prior CHOP induction by MMS was indirect via ER stress. Temperature-sensitive mutant cell lines (CHO K12, BHK tsBN7); BiP/GRP78 overexpression; stress-agent panel; gene expression analysis Molecular and cellular biology High 8754828
1996 Ectopic expression of CHOP (GADD153) induces apoptosis in M1 myeloblastic leukemia cells (>60% cell death at 72h) in a p53-independent manner. Apoptosis requires the leucine zipper domain but neither the intact basic region nor the trans-activation domain. CHOP-mediated apoptosis is accompanied by downregulation of Bcl-2 mRNA, and Bcl-2 overexpression delays the process. Conditional CHOP expression in M1 cells; site-directed mutagenesis of CHOP domains; Bcl-2 overexpression rescue; apoptosis assays FEBS letters High 8898082
1996 GADD153 (CHOP/DDIT3) forms endogenous heterodimers with C/EBP-beta in arsenite-treated PC12 cells, as demonstrated by co-immunoprecipitation. GADD153 overexpression inhibits C/EBP-beta-mediated transactivation of the GADD153 promoter, establishing an autoregulatory feedback loop in which GADD153 attenuates its own expression during stress via sequestration of C/EBP-beta. Co-immunoprecipitation of endogenous proteins from arsenite-treated PC12 cells; transient transfection reporter assays; EMSA The Journal of biological chemistry High 8662954
1996 GADD153 (CHOP) inhibits C/EBP transcriptional activity in 32D cl3 myeloid cells when overexpressed, reducing trans-activation by endogenous C/EBPs. High-level CHOP expression sensitizes cells to apoptosis when cells are transferred to G-CSF, suggesting CHOP-mediated inhibition of C/EBP-dependent survival signals. Ectopic CHOP overexpression in 32D cl3 cells; trans-activation assays; apoptosis assays under IL-3 vs G-CSF conditions Cancer research Medium 8764117
1996 ATF3 forms a non-functional heterodimer with GADD153/Chop10 (DDIT3): the ATF3-GADD153 heterodimer does not bind the ATF/CRE consensus site and does not repress transcription, in contrast to the ATF3 homodimer. This provides a mechanism by which GADD153 inhibits ATF3 function. Heterodimerization assays; DNA binding assays; transcriptional repression assays in transfected cells Molecular and cellular biology High 8622660
1997 ATF3 represses the expression of its inhibitor gadd153/Chop10 (DDIT3) by binding to two sites in the GADD153 promoter: an AP-1 site and a C/EBP-ATF composite site. ATF3 overexpression reduces endogenous GADD153 mRNA, establishing a mutual negative regulatory loop between ATF3 and GADD153. Promoter-reporter transfection assays; in vitro transcription assay; EMSA mapping of two ATF3 binding sites in GADD153 promoter; overexpression of ATF3 with endogenous GADD153 mRNA measurement; in vivo CCl4 model Molecular and cellular biology High 9343434
1999 CHOP (GADD153) interacts with ribosomal protein FTE/S3a (non-C/EBP binding partner). Bacterially expressed His-CHOP and in vitro translated FTE/S3a-Gal4 fusion protein co-immunoprecipitated with anti-CHOP antibodies; endogenous co-IP in Rauscher erythroleukemia cells confirmed the in vivo interaction. CHOP and FTE/S3a co-localize in both cytosol and nuclei. FTE/S3a overexpression inhibits erythroid differentiation, and this inhibition is reversed by simultaneous CHOP overexpression. Bacterially expressed protein co-immunoprecipitation; endogenous co-IP; Western blot co-localization; functional differentiation rescue assay The Journal of biological chemistry High 10713066
2000 CHOP (GADD153) physically interacts with TCF transcription factors, preventing TCF from binding its DNA recognition site, thereby inhibiting Wnt/TCF-dependent transcription. In Xenopus embryos, CHOP mRNA injection suppresses dorsal organizer formation and inhibits secondary axis induction by Wnt-8, Dishevelled, beta-catenin, or TCF-VP16. This inhibitory function requires the N-terminal transactivation domain of CHOP, not the C-terminal dimerization domain. CHOP-TCF binding assay; TCF-dependent luciferase reporter assays in human cell lines; Xenopus embryo injection; domain deletion mutants of CHOP Oncogene High 16434966
2004 TRAF7 specifically interacts with MEKK3 and potentiates MEKK3-mediated CHOP (DDIT3) and AP1 activation. Depletion of TRAF7 by antisense RNA inhibits MEKK3-mediated CHOP activation. Domain mapping shows TRAF7 potentiates CHOP activation and induces apoptosis through distinct domains. Co-immunoprecipitation; antisense RNA depletion; reporter assays for CHOP activation; domain mapping The Journal of biological chemistry Medium 15001576
2006 CHOP (DDIT3) forms heterodimers with C/EBP-beta and inhibits both the DNA-binding activity and Runx2-binding activity of C/EBP-beta, leading to inhibition of osteocalcin gene transcription and inhibition of osteoblast differentiation. CHOP-deficient osteoblasts differentiate more strongly than wild-type counterparts. Overexpression of CHOP in primary osteoblasts; CHOP-knockout osteoblast differentiation assays (alkaline phosphatase, calcified nodule formation); heterodimerization assay; DNA binding/Runx2-binding inhibition assays; reporter assay for osteocalcin promoter Molecular and cellular biology High 16880521
2006 CHOP/DDIT3 overexpression in osteoblastic ST-2 stromal cells (retroviral transduction) enhances osteoblastic differentiation, accelerates mineralized nodule formation, and increases osteocalcin/alkaline phosphatase expression. CHOP overexpression decreases C/EBP binding to consensus sequences by interacting with C/EBP alpha and beta (confirmed by EMSA/supershift assay), and enhances BMP-2/Smad signaling. Retroviral overexpression; EMSA/supershift assays for C/EBP interaction; Smad signaling assays; differentiation marker expression Endocrinology Medium 14684614
2009 DDIT3 (CHOP) and the fusion oncoprotein FUS-DDIT3 both bind cyclin-dependent kinase 2 (CDK2). In addition, CDK2 showed increased affinity for cytoskeletal proteins in cells expressing FUS-DDIT3 and DDIT3. Co-immunoprecipitation; interaction screen for CDK2 binding among G1 cyclins and CDKs BMC cell biology Medium 20017906
2010 CHOP (GADD153) physically interacts with the AP-1 complex protein c-Jun upon palmitate treatment; a CHOP:phospho-c-Jun heteromeric complex binds to the AP-1 consensus binding sequence in the PUMA promoter. CHOP knockdown reduces PUMA induction and Bax activation and attenuates palmitate-induced apoptosis. No functional CHOP binding sites were identified in the PUMA promoter, but CHOP acts via cooperation with AP-1. Co-immunoprecipitation of CHOP and phospho-c-Jun; ChIP with PUMA promoter AP-1 site; shRNA knockdown of CHOP; PUMA mRNA/protein and Bax activation assays American journal of physiology. Gastrointestinal and liver physiology High 20430872
2008 CHOP10 (DDIT3) associates with JDP2 via leucine zipper motifs; the JDP2-CHOP10 complex binds TPA response elements (TRE) both in vitro and in vivo (but not CRE sites) and strongly activates TRE-dependent transcription. JDP2 overexpression counteracts CHOP10 pro-apoptotic activity and increases cell viability following ER stress. Co-immunoprecipitation; in vitro and in vivo DNA binding assays; luciferase reporter assays; domain mapping; cell viability assay under ER stress Nucleic acids research Medium 18463134
2011 CHOP (DDIT3) directly regulates miR-708 expression: CHOP and miR-708 are co-encoded (miR-708 is within an intron of the CHOP-regulated gene Odz4) and co-expressed in brain and eye. CHOP-dependent miR-708 induction during ER stress is functionally validated—miR-708 directly targets rhodopsin mRNA, reducing rhodopsin protein levels through loss- and gain-of-function experiments. Genome-wide miRNA expression profiling; bioinformatics; miR-708 loss- and gain-of-function experiments; rhodopsin target validation; CHOP-dependent co-regulation assays The Journal of cell biology High 21402790
2012 DDIT3 (CHOP) has distinct cytoplasmic and nuclear functions: cytoplasmic DDIT3 inhibits cell migration and regulates 94 target genes; nuclear DDIT3 causes G1 cell cycle arrest and regulates 81 additional genes. Only 3 genes are regulated by both localizations. Promoters of target genes show no common sequence motifs, indicating DDIT3 acts via different heterodimer partners in each compartment. Tamoxifen-inducible DDIT3 expression constructs with cytoplasmic vs nuclear localization; genome-wide microarray expression analysis; cell migration assays; cell cycle analysis PloS one High 22496745
2012 RNase L associates with CHOP10 (DDIT3) mRNA and regulates its stability; in RNase L knockout MEFs, CHOP10 mRNA is stabilized, maintaining preadipocyte state and impairing terminal adipocyte differentiation. Ectopic RNase L restores CHOP10 mRNA instability and rescues adipocyte differentiation, lipid storage, and insulin sensitivity. RNase L-knockout MEFs; RNase L-CHOP10 mRNA association assay; ectopic RNase L rescue; CHOP10 siRNA in knockout cells; in vivo aged RNase L KO mice Cell death and differentiation High 22441668
2014 DDIT3 (CHOP) is a bona fide substrate for the SPOP-CUL3-RBX1 E3 ubiquitin ligase complex; SPOP recognizes a Ser/Thr-rich degron in the transactivation domain of DDIT3 and triggers its degradation via the ubiquitin-proteasome pathway. Prostate cancer-associated mutants of SPOP are defective in promoting DDIT3 degradation. Ubiquitination assays; proteasome inhibitor experiments; SPOP interaction/binding assays; degron mapping; prostate cancer SPOP mutant analysis Human mutation High 24990631
2016 CHOP/GADD153 (DDIT3)-dependent apoptosis involves direct CHOP-mediated induction of miR-216b expression. miR-216b accumulation requires PERK-dependent induction of CHOP and is antagonized by IRE1. miR-216b directly targets c-Jun mRNA, thereby reducing AP-1-dependent transcription and sensitizing cells to ER stress-dependent apoptosis. CHOP loss-of-function; PERK pathway analysis; IRE1 modulation; miR-216b gain/loss of function; c-Jun targeting validation; AP-1 reporter assays Nature communications High 27173017
2017 DDIT3 (CHOP) and JUN are independently regulated pro-death signaling molecules in retinal ganglion cells (RGCs) after optic nerve crush. Combined deficiency of Jun and Ddit3 provides significantly greater long-term RGC somal protection than either single knockout; Ddit3 deficiency does not alter JUN expression after injury, indicating the two pathways are independent. Despite somal protection, combined loss does not prevent axonal degeneration. Single and double knockout mice (Jun-/-, Ddit3-/-, Jun/Ddit3-/-); optic nerve crush model; RGC survival quantification at multiple time points; compound action potential recordings for axonal assessment Molecular neurodegeneration High 28969695
2021 DDIT3 (CHOP) acts as a rheostat that attenuates prolonged ISR (integrated stress response) during mitochondrial dysfunction by interacting with C/EBPβ to adjust ATF4 levels. CHOP-C/EBPβ interaction prevents overactivation of the ATF4-regulated transcriptional program. Failure of this interaction switches ISR from acute to chronic state, causing respiratory chain deficiency, energy crisis, and premature death. This identifies a role for CHOP as an attenuator (not activator) of mitochondrial stress response. Transgenic mice with mitochondrial cardiomyopathy; CHOP-C/EBPβ interaction studies; ATF4 level measurements; metabolic analysis; translation efficiency (Ribo-Seq/RNA-Seq); cardiac function assessment Science advances High 34039602
2021 DDIT3 (CHOP) directs a dual metabolic mechanism during glutamine deprivation: (1) nuclear DDIT3 promotes glycolysis and ATP production by suppressing the negative glycolytic regulator TIGAR; (2) a pool of DDIT3 translocates to mitochondria and suppresses oxidative phosphorylation through LONP1-mediated down-regulation of COQ9 and COX4, thereby dampening reactive oxygen species from glutamine withdrawal. DDIT3 induction during glutamine deprivation; TIGAR suppression assay; subcellular fractionation showing mitochondrial DDIT3 localization; LONP1 interaction; COQ9/COX4 regulation; metabolic flux analysis Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 34105294
2021 DDIT3 (CHOP) inhibits innate antiviral immunity via a DDIT3-OTUD1-MAVS pathway: DDIT3 promotes NF-κB-dependent OTUD1 expression; OTUD1 deubiquitinates and stabilizes Smurf1; Smurf1 then degrades MAVS via ubiquitination, ultimately suppressing type I interferon production. DDIT3 knockout in mice promotes antiviral innate immune response. DDIT3 overexpression/knockdown; NF-κB pathway analysis; OTUD1 deubiquitination assay; Smurf1 stabilization; MAVS ubiquitination/degradation assay; DDIT3 KO mice with BVDV infection Journal of virology Medium 33361422
2021 Chop/Ddit3 depletion in pancreatic β cells reduces ER Ca2+ buffering capacity and modulates glucose-induced islet Ca2+ oscillations, leading to transcriptional changes of ER chaperone profile ('ER remodeling'), delayed glucose-stimulated insulin secretion, and prevention of liver steatosis in HFD-fed mice. A GLP1-conjugated Chop antisense oligonucleotide recapitulates these effects. β cell-specific Chop knockout mice; HFD model; Ca2+ flux measurements in islets; ER chaperone expression profiling; liver triglyceride quantification; GLP1-ASO therapeutic approach Science translational medicine High 34321322
2022 The FUS::DDIT3 fusion oncoprotein inhibits BAF (mSWI/SNF) complex-mediated chromatin remodeling at adipogenic enhancer sites by sequestering the adipogenic transcription factor CEBPB from the genome. BAF chromatin occupancy and gene expression in FUS::DDIT3-expressing cells resembles SMARCB1-deficient tumor types. Co-immunoprecipitation (CEBPB sequestration); ChIP-seq for BAF complex occupancy; ATAC-seq for chromatin accessibility; transcriptome sequencing; small-molecule BAF ATPase inhibition; FUS::DDIT3 knockdown Molecular cell High 35390276
2023 TXNIP protein associates with the α-helix domain of CHOP (DDIT3) via its C-terminus, decreasing CHOP ubiquitination and increasing CHOP protein stability. In NASH, accumulation of TXNIP (due to impaired NEDD4L-mediated ubiquitination) leads to elevated CHOP protein levels (not mRNA). Knockdown of Txnip in NASH mouse livers suppresses CHOP expression and downstream apoptotic signaling. Co-immunoprecipitation (TXNIP-CHOP); ubiquitination assays for CHOP; gain-/loss-of-function studies in vitro and in vivo; NASH mouse models; adenovirus-mediated Txnip shRNA liver knockdown Theranostics High 37153733
2011 Chop (Ddit3) is essential for D469del-COMP retention and premature chondrocyte cell death in pseudoachondroplasia; crossing the D469del-COMP transgenic mouse onto a Chop null background alleviates both D469del-COMP intracellular retention and premature chondrocyte cell death, placing CHOP as a critical effector of ER stress-induced mutant protein retention. D469del-COMP transgenic mouse crossed with Chop-null (Ddit3-null) mice; immunostaining; transcriptome analysis; qRT-PCR; apoptosis assays The American journal of pathology High 22154935
2005 FUS-DDIT3 fusion oncogene induces C/EBPβ-mediated IL-6 expression in fibrosarcoma cells; siRNA knockdown of CEBPB transcripts abolishes the effect of FUS-DDIT3 on IL-6 expression. Chromatin immunoprecipitation reveals direct interaction between the IL-6 promoter and C/EBPβ in DDIT3/FUS-DDIT3-expressing cells. DDIT3 and FUS-DDIT3 show opposite effects on IL-8 transcription. Stable transfection of DDIT3-GFP and FUS-DDIT3-GFP; microarray; siRNA knockdown of CEBPB; RT-PCR; ChIP for C/EBPβ at IL-6 promoter International journal of cancer High 15688424
2004 The GADD153 promoter is transactivated by ETS1 and FLI-1 transcription factors via a single EBS (ETS binding site) in the human GADD153 promoter. ETS1 and FLI-1 strongly activate GADD153 EBS-linked reporter transcription; ETS2 produces only weak induction. Promoter-reporter (CAT) assays; EMSA for ETS1/FLI-1 binding to GADD153 EBS; ectopic expression of ETS1, ETS2, FLI-1 Cell death and differentiation Medium 10510472
2004 CHOP (GADD153) protein binds to and inhibits the CHOP promoter's C/EBP-binding site by interacting with C/EBP-beta, providing an autoregulatory loop. In aged rat hepatocytes, higher baseline GADD153/CHOP expression is correlated with enhanced JNK activation and greater sensitivity to ER stress-induced cell death; pharmacologic JNK inhibition decreases GADD153 expression, while p38 inhibition enhances it. Hepatocyte isolation from young and aged rats; ER stress inducers (TG, TM); JNK and p38 pharmacological inhibitors; GADD153 expression measurement; cell death assays Experimental gerontology Medium 15130668
2021 DDIT3/CHOP directly binds the SIRT1 promoter to promote its transcription (demonstrated by ChIP); SIRT1 then enhances autophagic activity. DDIT3-induced autophagy in ATDC5 chondrocytes proceeds via the SIRT1-AKT pathway, as SIRT1 inhibition or knockdown reverses DDIT3 overexpression effects on autophagy markers (Beclin1, LC3B, p62). DDIT3/CHOP KO mice show decreased autophagic markers in tibial growth plate. ChIP assay for DDIT3 binding to SIRT1 promoter; qRT-PCR; Western blot; DDIT3 overexpression/knockdown in ATDC5 cells; DDIT3 KO mice; autophagic flux assay with chloroquine; SIRT1 inhibitor/activator experiments Biochimica et biophysica acta. Molecular cell research High 34087318
2019 DDIT3/CHOP contributes to retinal photoreceptor cell degeneration induced by high-level HMOX1 expression via ER stress; genetic deletion of Ddit3 in knockout mice prevents photoreceptor cell degeneration caused by high-level HMOX1, placing DDIT3 downstream of HMOX1-induced ER stress. AAV-mediated HMOX1 overexpression at two doses; Ddit3 knockout mice; RNA-seq; qPCR; Western blot; TUNEL assay; ERG; immunostaining Molecular neurodegeneration High 33691741
2022 CHOP (DDIT3) up-regulation induced by albuminuria drives TXNIP shuttling from nucleus to mitochondria, where TXNIP promotes mitochondrial ROS production, oxidizes Trx2, liberates TXNIP to activate NLRP3 inflammasome and ASK1-dependent apoptosis. CHOP deletion (Chop-/- mice) suppresses TXNIP mitochondrial translocation, NLRP3 inflammasome activation, and p-ASK1-dependent apoptosis in nephrotic syndrome. Chop-/- and Txnip-/- mice; nephrotic syndrome model; subcellular fractionation of TXNIP; 68Ga-Galuminox molecular imaging of mitochondrial ROS; NLRP3/ASK1 activation assays Proceedings of the National Academy of Sciences of the United States of America High 35994650
1999 The CHOP and methionyl-tRNA synthetase (MetRS) genes overlap tail-to-tail at the 12q13 locus over a 55-bp region sharing complementary 3' UTR sequence containing an AU-rich element (ARE) that controls mRNA stability. The CHOP 3'UTR confers lower reporter activity than controls, and deleting the overlapping MetRS-complementary region increases reporter activity, demonstrating functional mRNA destabilization by the ARE. PCR mapping of gene overlap; luciferase reporter assay with CHOP 3'UTR constructs; deletion mutagenesis; transfection in NIH-3T3 cells Biochemical and biophysical research communications Medium 10448063
2001 NF-κB (p65 subunit specifically, not p50) represses GADD153/CHOP promoter activity, providing a cellular defense against ER stress-induced apoptosis. p65-/- MEFs show greater GADD153 expression and increased sensitivity to ER stress agents; transient transfection assays confirm p65 represses the GADD153 promoter. Transient transfection GADD153 promoter-reporter assays; p65-/- knockout MEFs; pharmacological NF-κB inhibitor (parthenolide); cell viability assays Oncogene High 11360202
1996 The EWS gene N-terminal region can substitute for the FUS N-terminal region in a CHOP fusion oncoprotein in myxoid liposarcoma, establishing that the oncogenic potential resides in the CHOP portion and that the two N-terminal FUS/EWS domains have common or similar oncogenic potential when fused to CHOP. Identification of EWS/CHOP chimeric gene by translocation analysis t(12;22); molecular cloning of EWS-CHOP fusion transcript in two MLS cases Oncogene Medium 8637704
2017 FUS-DDIT3 fusion oncoprotein drives aberrant IGF-IR/PI3K/Akt pathway activity through transcriptional induction of the IGF2 gene; RNAi-mediated FUS-DDIT3 knockdown in myxoid liposarcoma cells leads to inactivation of IGF-IR/PI3K/Akt signaling with diminished IGF2 mRNA expression. FUS-DDIT3 overexpression and RNAi knockdown; IGF2 mRNA quantification; IGF-IR/PI3K/Akt pathway signaling readouts; IGF-IR inhibitor treatment in vitro and in vivo (CAM model) Clinical cancer research Medium 28637688

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. The New England journal of medicine 4490 11807147
2004 Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell death and differentiation 2436 14685163
2019 The C/EBP Homologous Protein (CHOP) Transcription Factor Functions in Endoplasmic Reticulum Stress-Induced Apoptosis and Microbial Infection. Frontiers in immunology 933 30662442
1993 Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature 799 8510758
1996 Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP Kinase. Science (New York, N.Y.) 750 8650547
1996 Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP/GADD153). Molecular and cellular biology 592 8754828
1994 CHOP (GADD153) and its oncogenic variant, TLS-CHOP, have opposing effects on the induction of G1/S arrest. Genes & development 297 8125258
1996 Ectopic expression of CHOP (GADD153) induces apoptosis in M1 myeloblastic leukemia cells. FEBS letters 273 8898082
1996 Analysis of ATF3, a transcription factor induced by physiological stresses and modulated by gadd153/Chop10. Molecular and cellular biology 264 8622660
2021 Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL. Cancer cell 256 34739844
1996 Fusion of the EWS and CHOP genes in myxoid liposarcoma. Oncogene 237 8637704
1995 Inhibition of adipogenesis by the stress-induced protein CHOP (Gadd153). The EMBO journal 210 7588595
2019 Artesunate activates the ATF4-CHOP-CHAC1 pathway and affects ferroptosis in Burkitt's Lymphoma. Biochemical and biophysical research communications 173 31537387
2021 Romidepsin Plus CHOP Versus CHOP in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Results of the Ro-CHOP Phase III Study (Conducted by LYSA). Journal of clinical oncology : official journal of the American Society of Clinical Oncology 164 34843406
2010 CHOP and AP-1 cooperatively mediate PUMA expression during lipoapoptosis. American journal of physiology. Gastrointestinal and liver physiology 155 20430872
2004 TRAF7 potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis. The Journal of biological chemistry 147 15001576
1997 gadd153/Chop10, a potential target gene of the transcriptional repressor ATF3. Molecular and cellular biology 141 9343434
1996 GADD153/CHOP, a DNA damage-inducible protein, reduced CAAT/enhancer binding protein activities and increased apoptosis in 32D c13 myeloid cells. Cancer research 137 8764117
1998 Transcription factors C/EBP alpha, C/EBP beta, and CHOP (Gadd153) expressed during the differentiation program of keratinocytes in vitro and in vivo. The Journal of investigative dermatology 123 9506442
2000 Upregulation of BiP and CHOP by the unfolded-protein response is independent of presenilin expression. Nature cell biology 118 11146649
2021 Adaptation to mitochondrial stress requires CHOP-directed tuning of ISR. Science advances 117 34039602
2015 Long noncoding RNA HOXA-AS2 promotes gastric cancer proliferation by epigenetically silencing P21/PLK3/DDIT3 expression. Oncotarget 106 26384350
2012 Distinct cytoplasmic and nuclear functions of the stress induced protein DDIT3/CHOP/GADD153. PloS one 102 22496745
2001 Repression of GADD153/CHOP by NF-kappaB: a possible cellular defense against endoplasmic reticulum stress-induced cell death. Oncogene 101 11360202
1996 Physical and functional association between GADD153 and CCAAT/enhancer-binding protein beta during cellular stress. The Journal of biological chemistry 101 8662954
2011 A CHOP-regulated microRNA controls rhodopsin expression. The Journal of cell biology 91 21402790
2004 Elevated gadd153/chop expression and enhanced c-Jun N-terminal protein kinase activation sensitizes aged cells to ER stress. Experimental gerontology 88 15130668
2016 miR-216b regulation of c-Jun mediates GADD153/CHOP-dependent apoptosis. Nature communications 78 27173017
2008 Chop it, ChIP it, check it: the current status of chromatin immunoprecipitation. Frontiers in bioscience : a journal and virtual library 78 17981601
2002 GADD153 and 12-lipoxygenase mediate fenretinide-induced apoptosis of neuroblastoma. Cancer research 78 12234979
2020 Alemtuzumab plus CHOP versus CHOP in elderly patients with peripheral T-cell lymphoma: the DSHNHL2006-1B/ACT-2 trial. Leukemia 77 32382083
2021 DDIT3 Directs a Dual Mechanism to Balance Glycolysis and Oxidative Phosphorylation during Glutamine Deprivation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 76 34105294
2006 CCAAT/enhancer-binding protein homologous protein (CHOP) regulates osteoblast differentiation. Molecular and cellular biology 75 16880521
2021 DDIT3 Immunohistochemistry Is a Useful Tool for the Diagnosis of Myxoid Liposarcoma. The American journal of surgical pathology 73 32815829
2003 CCAAT/enhancer binding protein homologous protein (DDIT3) induces osteoblastic cell differentiation. Endocrinology 73 14684614
2015 A STAT3-NFkB/DDIT3/CEBPβ axis modulates ALDH1A3 expression in chemoresistant cell subpopulations. Oncotarget 69 25868979
2006 The myxoid/round cell liposarcoma fusion oncogene FUS-DDIT3 and the normal DDIT3 induce a liposarcoma phenotype in transfected human fibrosarcoma cells. The American journal of pathology 68 16651630
2021 Chop/Ddit3 depletion in β cells alleviates ER stress and corrects hepatic steatosis in mice. Science translational medicine 67 34321322
1999 Urea-associated oxidative stress and Gadd153/CHOP induction. The American journal of physiology 66 10330061
2020 Cardiovascular adverse events in patients with non-Hodgkin lymphoma treated with first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP with rituximab (R-CHOP): a systematic review and meta-analysis. The Lancet. Haematology 64 32135128
2015 C/EBP homologous protein (CHOP) gene deficiency attenuates renal ischemia/reperfusion injury in mice. Biochimica et biophysica acta 63 26071644
2009 CHOP and the endoplasmic reticulum stress response in myelinating glia. Current opinion in neurobiology 62 19744850
2017 Together JUN and DDIT3 (CHOP) control retinal ganglion cell death after axonal injury. Molecular neurodegeneration 61 28969695
2006 Elevated gadd153/chop expression during resveratrol-induced apoptosis in human colon cancer cells. Biochemical pharmacology 61 17049495
2021 DDIT3 Targets Innate Immunity via the DDIT3-OTUD1-MAVS Pathway To Promote Bovine Viral Diarrhea Virus Replication. Journal of virology 60 33361422
2012 Association between arsenic suppression of adipogenesis and induction of CHOP10 via the endoplasmic reticulum stress response. Environmental health perspectives 59 23221991
2006 Expression and function of C/EBP homology protein (GADD153) in podocytes. The American journal of pathology 55 16400006
2022 Blocking CHOP-dependent TXNIP shuttling to mitochondria attenuates albuminuria and mitigates kidney injury in nephrotic syndrome. Proceedings of the National Academy of Sciences of the United States of America 54 35994650
1997 The growth arrest genes gas5, gas6, and CHOP-10 (gadd153) are expressed in the mouse preimplantation embryo. Molecular reproduction and development 53 9322241
2006 The C/EBP homologous protein CHOP (GADD153) is an inhibitor of Wnt/TCF signals. Oncogene 50 16434966
2014 Rosemary (Rosmarinus officinalis) extract modulates CHOP/GADD153 to promote androgen receptor degradation and decreases xenograft tumor growth. PloS one 45 24598693
2005 Myxoid liposarcoma FUS-DDIT3 fusion oncogene induces C/EBP beta-mediated interleukin 6 expression. International journal of cancer 45 15688424
2000 Novel interaction between the transcription factor CHOP (GADD153) and the ribosomal protein FTE/S3a modulates erythropoiesis. The Journal of biological chemistry 44 10713066
2005 Involvement of GADD153 and cardiac ankyrin repeat protein in hypoxia-induced apoptosis of H9c2 cells. The Journal of biological chemistry 43 15826945
2021 High dose expression of heme oxigenase-1 induces retinal degeneration through ER stress-related DDIT3. Molecular neurodegeneration 42 33691741
2021 Nuclear expression of DDIT3 distinguishes high-grade myxoid liposarcoma from other round cell sarcomas. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 41 33731886
2017 FUS-DDIT3 Fusion Protein-Driven IGF-IR Signaling is a Therapeutic Target in Myxoid Liposarcoma. Clinical cancer research : an official journal of the American Association for Cancer Research 40 28637688
2011 DDIT3 gene break-apart as a molecular marker for diagnosis of myxoid liposarcoma--assay validation and clinical experience. Diagnostic molecular pathology : the American journal of surgical pathology, part B 37 22089349
2011 Chop (Ddit3) is essential for D469del-COMP retention and cell death in chondrocytes in an inducible transgenic mouse model of pseudoachondroplasia. The American journal of pathology 37 22154935
2019 Endoplasmic Reticulum Stress Increases DUSP5 Expression via PERK-CHOP Pathway, Leading to Hepatocyte Death. International journal of molecular sciences 36 31491992
2013 CCAAT/enhancer-binding protein homologous (CHOP) protein promotes carcinogenesis in the DEN-induced hepatocellular carcinoma model. PloS one 36 24339898
2008 TRE-dependent transcription activation by JDP2-CHOP10 association. Nucleic acids research 35 18463134
2021 DDIT3/CHOP promotes autophagy in chondrocytes via SIRT1-AKT pathway. Biochimica et biophysica acta. Molecular cell research 33 34087318
1999 Regulated expression and functional role of the transcription factor CHOP (GADD153) in erythroid growth and differentiation. Blood 33 10233889
2022 DLBCL 1L-What to Expect beyond R-CHOP? Cancers 31 35326604
2014 Destruction of DDIT3/CHOP protein by wild-type SPOP but not prostate cancer-associated mutants. Human mutation 31 24990631
2010 Selenium decreases thyroid cancer cell growth by increasing expression of GADD153 and GADD34. Nutrition and cancer 30 20043261
2022 The FUS::DDIT3 fusion oncoprotein inhibits BAF complex targeting and activity in myxoid liposarcoma. Molecular cell 29 35390276
2004 Regulation of aldehyde reductase expression by STAF and CHOP. Genomics 29 14667815
2002 Activator protein-1 and CCAAT/enhancer-binding protein mediated GADD153 expression is involved in deoxycholic acid-induced apoptosis. Biochimica et biophysica acta 29 12069855
1999 Upregulation of CHOP-10 (gadd153) expression in the mouse blastocyst as a response to stress. Molecular reproduction and development 29 10542372
2022 Fusion protein-driven IGF-IR/PI3K/AKT signals deregulate Hippo pathway promoting oncogenic cooperation of YAP1 and FUS-DDIT3 in myxoid liposarcoma. Oncogenesis 28 35459264
2017 Isochaihulactone-induced DDIT3 causes ER stress-PERK independent apoptosis in glioblastoma multiforme cells. Oncotarget 28 27852055
2012 RNase L controls terminal adipocyte differentiation, lipids storage and insulin sensitivity via CHOP10 mRNA regulation. Cell death and differentiation 28 22441668
2005 Understanding mesenchymal cancer: the liposarcoma-associated FUS-DDIT3 fusion gene as a model. Seminars in cancer biology 26 15826835
1999 CHOP/GADD153 and methionyl-tRNA synthetase (MetRS) genes overlap in a conserved region that controls mRNA stability. Biochemical and biophysical research communications 26 10448063
2021 DA-R-EPOCH vs R-CHOP in DLBCL: How do we choose? Clinical advances in hematology & oncology : H&O 25 34807015
2000 Phaco-chop versus stop-and-chop nucleotomy for phacoemulsification. Journal of cataract and refractive surgery 25 11084272
2002 Expression and transactivating functions of the bZIP transcription factor GADD153 in mammary epithelial cells. Oncogene 24 12082616
1996 Quinone thioether-mediated DNA damage, growth arrest, and gadd153 expression in renal proximal tubular epithelial cells. Molecular pharmacology 24 8794898
2020 DDIT3 modulates cancer stemness in gastric cancer by directly regulating CEBPβ. The Journal of pharmacy and pharmacology 23 32189359
2013 A crosstalk between p21 and UPR-induced transcription factor C/EBP homologous protein (CHOP) linked to type 2 diabetes. Biochimie 23 24239558
2010 Methylation status of DDIT3 gene in chronic myeloid leukemia. Journal of experimental & clinical cancer research : CR 23 20492726
2006 Doxazosin induces activation of GADD153 and cleavage of focal adhesion kinase in cardiomyocytes en route to apoptosis. Cardiovascular research 23 16631627
2020 A perspective on improving the R-CHOP regimen: from Mega-CHOP to ROBUST R-CHOP, the PHOENIX is yet to rise. The Lancet. Haematology 22 33091357
2019 DDIT3 (CHOP) contributes to retinal ganglion cell somal loss but not axonal degeneration in DBA/2J mice. Cell death discovery 22 31632741
2020 Homocysteine induces melanocytes apoptosis via PERK-eIF2α-CHOP pathway in vitiligo. Clinical science (London, England : 1979) 21 32400851
2009 Regulation of GADD153 induced by mechanical stress in cardiomyocytes. European journal of clinical investigation 21 19614958
2023 A novel NEDD4L-TXNIP-CHOP axis in the pathogenesis of nonalcoholic steatohepatitis. Theranostics 20 37153733
2009 DDIT3/CHOP and the sarcoma fusion oncoprotein FUS-DDIT3/TLS-CHOP bind cyclin-dependent kinase 2. BMC cell biology 20 20017906
2003 Induction of GADD153 and Bak: novel molecular targets of fenretinide-induced apoptosis of neuroblastoma. Cancer letters 20 12880976
1999 Regulation of the human stress response gene GADD153 expression: role of ETS1 and FLI-1 gene products. Cell death and differentiation 20 10510472
2022 DDIT3/CHOP mediates the inhibitory effect of ER stress on chondrocyte differentiation by AMPKα-SIRT1 pathway. Biochimica et biophysica acta. Molecular cell research 19 35381294
2016 Crosstalk between C/EBP homologous protein (CHOP) and glucocorticoid receptor in lung cancer. Molecular and cellular endocrinology 19 27496643
2014 DDIT3 overexpression increases odontoblastic potential of human dental pulp cells. Cell proliferation 19 24738922
2001 DNA damaging agents increase gadd153 (CHOP-10) messenger RNA levels in bovine preimplantation embryos cultured in vitro. Biology of reproduction 19 11319142
2017 FXR controls CHOP expression in steatohepatitis. FEBS letters 18 28895119
2019 C/EBP Homologous Protein (CHOP) Activates Macrophages and Promotes Liver Fibrosis in Schistosoma japonicum-Infected Mice. Journal of immunology research 17 31886304
2010 Nuclear expression of FLT1 and its ligand PGF in FUS-DDIT3 carrying myxoid liposarcomas suggests the existence of an intracrine signaling loop. BMC cancer 17 20515481
2009 Involvement of GADD153 and cardiac ankyrin repeat protein in cardiac ischemia-reperfusion injury. Experimental & molecular medicine 17 19299913

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