Affinage

ATF5

Cyclic AMP-dependent transcription factor ATF-5 · UniProt Q9Y2D1

Length
282 aa
Mass
30.7 kDa
Annotated
2026-04-28
100 papers in source corpus 41 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATF5 is a stress-responsive bZIP transcription factor that integrates cellular stress signals to control survival, differentiation, and organelle quality across diverse tissues. Its expression is regulated at multiple levels: translationally via eIF2α phosphorylation-dependent bypass of inhibitory uORFs in its 5′-UTR, with an additional nonsense-mediated mRNA decay layer targeting uORF2-containing transcripts (PMID:18195013, PMID:18055463, PMID:23876217); and post-translationally via N-terminal ubiquitinylation by the E2 enzyme Cdc34, counteracted by HSP70-mediated stabilization and NLK/TAK1-dependent protection from proteasomal degradation (PMID:18458088, PMID:21521685, PMID:25512613). As a transcription factor, ATF5 activates pro-survival targets including MCL1 and BCL-2 downstream of oncogenic (RAS/MAPK–CREB3L2, BCR-ABL/PI3K/AKT) and stress (mitochondrial UPR, ER stress) signaling pathways, while also functioning as a structural centrosomal protein that forms a 9-fold ring at the mother centriole to scaffold pericentriolar material assembly in a SUMOylation-regulated, cell-cycle-dependent manner (PMID:20495567, PMID:21212266, PMID:27426517, PMID:26213385, PMID:29326161).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2003 High

    Establishing ATF5 as a neural progenitor maintenance factor resolved how bZIP transcription factors control the proliferation-to-differentiation switch in neurogenesis.

    Evidence Overexpression, dominant-negative, and siRNA approaches in PC12 cells and neurosphere cultures with NGF treatment

    PMID:12805299

    Open questions at the time
    • Direct transcriptional targets mediating the anti-differentiation effect were not identified
    • No in vivo loss-of-function model at that time
  2. 2007 High

    Demonstrating that ATF5 translation is controlled by eIF2α phosphorylation-dependent bypass of inhibitory uORFs in its 5′-UTR established ATF5 as a member of the ISR-regulated translational program alongside ATF4.

    Evidence Luciferase reporters with uORF mutagenesis, eIF2α kinase overexpression, polyribosome fractionation in mammalian cells

    PMID:18055463 PMID:18195013

    Open questions at the time
    • Relative contributions of 5′-UTRα versus 5′-UTRβ in different tissues not resolved
    • Whether additional kinases beyond HRI regulate this switch in vivo
  3. 2008 High

    Identifying N-terminal ubiquitinylation via the E2 enzyme Cdc34 as the primary ATF5 degradation mechanism explained how ATF5 protein is kept at low steady-state levels and how genotoxic stress (cisplatin) stabilizes ATF5.

    Evidence Ubiquitination assays, N-terminal tagging, Cdc34 localization analysis, co-IP in mammalian cells

    PMID:18458088

    Open questions at the time
    • The E3 ubiquitin ligase responsible was not identified
    • Whether N-terminal ubiquitinylation applies in all cell types
  4. 2010 High

    A genome-wide RNAi screen placing ATF5 downstream of RAS-MAPK/CREB3L2 and upstream of MCL1 in glioma established the first oncogenic transcriptional cascade through which ATF5 promotes tumor survival.

    Evidence Genome-wide RNAi screen, ChIP, reporter assays, mouse xenograft models in malignant glioma

    PMID:20495567

    Open questions at the time
    • Whether CREB3L2–ATF5–MCL1 axis operates in non-glioma cancers
    • Structural basis of ATF5 binding to the MCL1 promoter
  5. 2011 High

    Multiple studies in 2011 defined a layered post-translational regulatory network: HSP70 stabilizes ATF5 against proteasomal/caspase degradation, p300 acetylates ATF5 at K29 to enhance promoter binding, and ATF5 directly transactivates BCL-2 and Egr-1, clarifying how ATF5 protein activity is fine-tuned and which survival genes it controls.

    Evidence Reciprocal co-IP with domain mapping and ATPase mutants (HSP70); in vitro acetylation, ChIP, and mutagenesis (p300/Egr-1); EMSA and ChIP for BCL-2 promoter binding

    PMID:21212266 PMID:21521685 PMID:21791614

    Open questions at the time
    • Whether acetylation and HSP70 binding are coordinated or competitive
    • Identity of deacetylase(s) reversing K29 acetylation
  6. 2011 High

    Linking BCR-ABL to ATF5-mediated mTOR transcription and autophagy suppression revealed an oncogene–ATF5–mTOR axis controlling autophagy in CML.

    Evidence ChIP, reporter assays, siRNA epistasis, pharmacological inhibition in BCR-ABL-transformed cells

    PMID:21715304

    Open questions at the time
    • Whether ATF5 activates mTOR transcription in non-leukemic contexts
    • Direct ATF5 binding site on the mTOR promoter not mapped at nucleotide resolution
  7. 2012 High

    NPM1 was identified as an ATF5 interactor that displaces HSP70 and promotes ATF5 polyubiquitination and degradation, with NPM1-c AML mutant failing to do so—connecting ATF5 stability to nucleolar integrity and AML pathogenesis.

    Evidence TAP-MS, co-IP, ubiquitination assays, NPM1-c mutant analysis

    PMID:22528486

    Open questions at the time
    • Whether NPM1-c-mediated ATF5 stabilization contributes to leukemogenesis in vivo
    • Stoichiometry of the HSP70–ATF5–NPM1 competition
  8. 2012 High

    Atf5 knockout mice revealed that ATF5 is essential for terminal differentiation and survival of olfactory sensory neurons, establishing a non-cancer developmental role.

    Evidence Atf5 knockout mice with OSN marker immunostaining and ectopic expression in neural progenitors

    PMID:23090999

    Open questions at the time
    • Direct transcriptional targets of ATF5 driving OSN fate commitment not comprehensively identified
    • Whether ATF5 cooperates with other bZIP factors in OSN specification
  9. 2013 High

    Two discoveries added regulatory depth: CHOP directly activates ATF5 transcription creating a feedforward pro-apoptotic loop during proteasome inhibition, and ATF5 mRNA is subject to NMD via uORF2, adding an mRNA stability layer to stress-responsive ATF5 induction.

    Evidence Promoter reporters and siRNA with cell viability readouts (CHOP); Upf1/Upf2 knockdown with uAUG2 mutagenesis and mRNA stability assays (NMD)

    PMID:23761072 PMID:23876217

    Open questions at the time
    • Whether NMD regulation of ATF5 contributes to tissue-specific expression patterns
    • Relative contribution of translational versus NMD regulation under different stresses
  10. 2015 High

    Super-resolution imaging revealed an entirely unexpected structural role: ATF5 forms a 9-fold symmetrical ring at the proximal end of the mother centriole, scaffolding PCM assembly through interactions with polyglutamylated tubulin and pericentrin, and its loss causes centriole fragmentation and genomic instability.

    Evidence Structured illumination microscopy, co-IP, siRNA knockdown, cell cycle synchronization

    PMID:26213385

    Open questions at the time
    • How a bZIP transcription factor structurally integrates into the centriole wall
    • Whether centrosomal and nuclear/transcriptional functions are coordinated or independent
  11. 2016 High

    ATF5 was established as the mammalian mediator of the mitochondrial UPR: normally sequestered in mitochondria, it accumulates in the cytosol and nucleus during mitochondrial stress, functionally rescuing C. elegans atfs-1 loss.

    Evidence Cell fractionation, C. elegans genetic rescue, knockdown with mitochondrial stress assays

    PMID:27426517

    Open questions at the time
    • Import/export mechanism controlling ATF5 mitochondrial sequestration
    • Whether ATF5 directly senses mitochondrial protein misfolding or responds to secondary signals
  12. 2018 High

    Demonstrating that SUMO2/3 modification of ATF5 dislodges it from the centrosome at the end of M phase resolved how the centrosomal and nuclear pools of ATF5 are cell-cycle-regulated.

    Evidence SUMO modification assay, SUMO-site mutagenesis, cell cycle synchronization, centrosome immunofluorescence

    PMID:29326161

    Open questions at the time
    • Identity of the SUMO E3 ligase and SENP deconjugase controlling ATF5 SUMOylation
    • Whether deSUMOylated ATF5 released from centrosomes enters the nucleus to function as a transcription factor
  13. 2019 High

    Unbiased pull-down/MS revealed that dominant-negative ATF5 kills tumor cells primarily by blocking CEBPB and CEBPD transcriptional activity rather than ATF5 alone, reinterpreting the mechanism of the anti-cancer DN-ATF5 tool.

    Evidence Pull-down with mass spectrometry, co-IP, siRNA knockdown, cell viability assays

    PMID:31676720

    Open questions at the time
    • Whether endogenous ATF5 normally heterodimerizes with CEBPB/CEBPD to regulate shared targets
    • Therapeutic implications require validation in patient-derived models
  14. 2019 High

    In vivo ischemia-reperfusion studies in Atf5−/− mice demonstrated that pharmacological UPRmt induction is cardioprotective in an ATF5-dependent manner, extending ATF5's UPRmt role to cardiac protection.

    Evidence Atf5 global knockout mice, ex vivo and in vivo cardiac ischemia-reperfusion models, RNA-Seq

    PMID:31274354

    Open questions at the time
    • ATF5-dependent cardioprotective gene targets not fully characterized
    • Whether ATF5 operates through the same mitochondria-to-nucleus translocation in cardiomyocytes
  15. 2022 High

    Atf5 KO mice revealed that ATF5 is required for mitochondrial quality control in skeletal muscle—governing mitophagy, antioxidant defense, and UPRmt gene induction during exercise—extending its organelle maintenance role beyond the heart.

    Evidence ATF5 KO mice, subcellular fractionation, mitochondrial respiration and ROS assays, exercise protocol

    PMID:36332794

    Open questions at the time
    • Whether exercise enrichment of ATF5 in mitochondrial fractions reflects import or membrane association
    • Tissue-specific versus systemic consequences of ATF5 loss on exercise adaptation
  16. 2022 High

    Conditional knockout studies showed ATF5 transcriptionally activates cholecystokinin to promote intestinal barrier function and satiety, revealing a gut endocrine role distinct from its stress-response functions.

    Evidence ATF5 conditional and global KO mice, enteric pathogen challenge, hormone measurements

    PMID:36516750

    Open questions at the time
    • Whether ATF5 directly binds the cholecystokinin promoter
    • How intestinal ATF5 expression is regulated
  17. 2023 High

    Identification of METTL1-mediated m7G methylation of Atf5 mRNA as a mechanism enhancing ATF5 expression, with ATF5 then activating the CDK inhibitor Inca1 to suppress cardiomyocyte proliferation, connected epitranscriptomics to ATF5-dependent cell cycle control in the heart.

    Evidence m7G MeRIP-seq, co-IP, ChIP, siRNA, in vivo myocardial injury model

    PMID:37286744

    Open questions at the time
    • Whether m7G modification of ATF5 mRNA occurs in non-cardiac contexts
    • Whether Inca1 is a direct or indirect ATF5 target in other proliferative tissues

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ATF5's dual roles as a nuclear transcription factor and a structural centrosomal protein are coordinated—including the signals partitioning ATF5 among mitochondria, centrosome, and nucleus, and the E3 ligase(s) controlling its N-terminal ubiquitinylation—remains unresolved.
  • E3 ubiquitin ligase for ATF5 not identified
  • Mechanism of ATF5 import into mitochondria and its release during stress unclear
  • Whether centrosomal ATF5 pool and transcription factor pool derive from distinct translation or post-translational sorting events

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 4 GO:0005198 structural molecule activity 1
Localization
GO:0005634 nucleus 4 GO:0005739 mitochondrion 2 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 1
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-8953897 Cellular responses to stimuli 6 R-HSA-392499 Metabolism of proteins 5 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3 R-HSA-1852241 Organelle biogenesis and maintenance 3 R-HSA-162582 Signal Transduction 2
Partners
CDC34CEBPBCEBPDEP300HSPA1ANLKNPM1PCNT

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 ATF5 mediates the mammalian mitochondrial unfolded protein response (UPRmt) by organelle partitioning: normally sequestered in mitochondria, ATF5 accumulates in the cytosol and traffics to the nucleus during mitochondrial stress to activate UPRmt transcriptional targets. ATF5 expression rescues UPRmt signaling in atfs-1-deficient C. elegans via the same UPRmt promoter element, demonstrating functional conservation. Cell fractionation, C. elegans genetic rescue, mammalian cell knockdown with mitochondrial stress assays, transcriptional reporter assays Current biology : CB High 27426517
2008 ATF5 protein expression is translationally upregulated in response to diverse stresses (ER stress, arsenite, proteasome inhibition) via eIF2α phosphorylation. The ATF5 5'-UTRα contains two uORFs analogous to ATF4: uORF1 is positive-acting allowing reinitiation, while uORF2 is inhibitory under normal conditions; eIF2 phosphorylation during stress permits ribosomes to bypass uORF2 and translate the ATF5 coding region. ATF4 also contributes to basal ATF5 mRNA transcription. Polyribosome fractionation, luciferase reporter mutagenesis of 5'-UTR uORFs, ATF4 knockout MEF analysis The Journal of biological chemistry High 18195013
2007 ATF5 mRNA translation is regulated by alternative 5'-UTRs (5'-UTRα and 5'-UTRβ): 5'-UTRα represses translation under normal conditions, and this repression is relieved by amino acid limitation or arsenite via eIF2α phosphorylation. Mutation of uAUG2 in uORF2 abolishes stress-induced translational upregulation. Luciferase reporter assay with 5'-UTR mutants, eIF2α phosphorylation analysis, heme-regulated inhibitor kinase overexpression The Journal of biological chemistry High 18055463
2013 CHOP directly induces ATF5 transcription in response to proteasome inhibition; ATF5 in turn activates pro-apoptotic targets including NOXA, creating a feedforward loop. Both ATF4 and CHOP directly transcriptionally activate ATF5. ATF5 knockdown increases cell survival during proteasome inhibition, indicating a pro-apoptotic function. Promoter reporter assays, siRNA knockdown, transcriptome analysis, cell viability assays Molecular biology of the cell High 23761072
2010 In malignant glioma, RAS-MAPK or PI3K signaling activates CREB3L2, which directly activates ATF5 transcription; ATF5 in turn promotes survival by stimulating transcription of MCL1, an anti-apoptotic BCL-2 family member. Genome-wide RNAi screen, chromatin immunoprecipitation, reporter assays, siRNA knockdown, mouse xenograft models Nature medicine High 20495567
2011 BCR-ABL suppresses autophagy through the PI3K/AKT/FOXO4 pathway, which transcriptionally upregulates ATF5; ATF5 then stimulates transcription of mTOR, a master negative regulator of autophagy. Imatinib-induced autophagy results from inhibition of this BCR-ABL/PI3K/AKT/FOXO4/ATF5/mTOR pathway. Reporter assays, ChIP, siRNA knockdown, pharmacological inhibition, BCR-ABL transformed cell lines Blood High 21715304
2003 ATF5 promotes neuroprogenitor cell expansion and blocks differentiation into neurons; NGF downregulates ATF5 protein and transcripts, and exogenous ATF5 suppresses NGF-promoted neurite outgrowth requiring CRE site repression. Dominant-negative ATF5 or siRNA targeting ATF5 accelerates neurogenesis. PC12 cell overexpression/knockdown, dominant-negative ATF5, siRNA, clonal neurosphere cultures, NGF treatment The Journal of neuroscience : the official journal of the Society for Neuroscience High 12805299
2011 BCL-2 is a direct downstream transcriptional target of ATF5: ATF5 binds to an ATF5-specific regulatory element downstream of the BCL-2 P2 promoter to stimulate BCL-2 expression in C6 glioma and MCF-7 breast cancer cells but not in non-transformed cells, explaining cell-type-dependent survival function. Promoter reporter assays, electrophoretic mobility shift assay (EMSA), ChIP, siRNA knockdown, dominant-negative ATF5 The Journal of biological chemistry High 21212266
2011 ATF5 interacts with the transcriptional coactivator p300, which acetylates ATF5 at lysine-29; this acetylation enhances ATF5-p300 interaction and binding to the ATF5 response element (ARE) in the Egr-1 promoter. The ATF5/p300 complex then acetylates histone H3 at K14 at both ARE and SRE regions, facilitating ERK-phosphorylated Elk-1 binding and activating Egr-1 transcription. Co-IP, in vitro acetylation assays, ChIP, mutagenesis of acetylation sites, reporter assays Molecular and cellular biology High 21791614
2011 HSP70 interacts with the N-terminal activation domain of ATF5 (which is proline-rich) in an ATP-driven, ATPase-dependent manner. HSP70 binding stabilizes ATF5 protein against proteasome- and caspase-dependent degradation; HSP70 depletion accelerates ATF5 degradation and reduces downstream BCL-2 and Egr-1 expression. Co-IP, overexpression/knockdown, proteasome inhibitor experiments, ATPase mutant HSP70 The Journal of biological chemistry High 21521685
2012 Nucleophosmin (NPM1/B23) was identified by tandem affinity purification/mass spectrometry as an ATF5-interacting protein; NPM1 binds ATF5 via its C-terminal region (nucleolar localization domain) interacting with the ATF5 bZIP domain. NPM1 binding promotes ATF5 polyubiquitination and degradation via proteasome- and caspase-dependent pathways, displacing HSP70 from ATF5. NPM1-c mutant lacking nucleolar localization fails to degrade ATF5. Tandem affinity purification, mass spectrometry, co-IP, ubiquitination assays, NPM1-c mutant analysis The Journal of biological chemistry High 22528486
2015 ATF5 forms a 9-fold symmetrical ring structure at the proximal end of the mother centriole in the inner layer of the pericentriolar material (PCM). ATF5 interacts with polyglutamylated tubulin on the mother centriole and with pericentrin (PCNT) in the PCM, controlling centriole-PCM interaction in a cell-cycle- and centriole-age-dependent manner. ATF5 depletion blocks PCM accumulation, causes centriole fragmentation, and leads to multipolar mitotic spindles and genomic instability. Super-resolution microscopy (structured illumination), co-IP, siRNA knockdown, cell cycle synchronization, immunofluorescence Cell High 26213385
2018 ATF5 is SUMO2/3-modified at a conserved consensus site; SUMOylation is elevated in G1 phase and diminished in G2/M phase. SUMOylation disrupts ATF5 interaction with centrosomal proteins and dislodges ATF5 from the centrosome at end of M phase. Blocking ATF5 SUMOylation deregulates the centrosome cycle, prevents ATF5 translocation from the centrosome, and causes genomic instability and G2/M arrest. SUMO modification assay, co-IP, cell cycle synchronization, mutagenesis of SUMO consensus site, centrosome localization by immunofluorescence The Journal of biological chemistry High 29326161
2008 ATF5 protein is degraded via the ubiquitin-proteasome pathway through N-terminal ubiquitinylation at the free amino group of the N-terminal methionine. Cisplatin stabilizes ATF5 by promoting nucleus-to-cytoplasm translocation of E2 ubiquitin-conjugating enzyme Cdc34, reducing the interaction between ATF5 and Cdc34. Ubiquitination assays, N-terminal tagging experiments, Cdc34 localization analysis, co-IP The Journal of biological chemistry High 18458088
2012 In glioma, the endoplasmic reticulum stress transducer BBF2H7 directly activates ATF5 transcription; ATF5 in turn activates MCL1 transcription to suppress ER stress-induced apoptosis in chondrocytes. Loss of BBF2H7 leads to loss of ATF5 and MCL1, and increased apoptosis in proliferating chondrocytes. Bbf2h7 knockout mice, reporter assays, ChIP, immunostaining, TUNEL The Journal of biological chemistry High 22936798
2019 Dominant-negative ATF5 (DN-ATF5) kills tumor cells by associating with and blocking the transcriptional activities of CEBPB and CEBPD (not exclusively ATF5 itself), as revealed by unbiased pull-down/mass spectrometry. CEBPB or CEBPD knockdown causes apoptosis of multiple cancer cell lines but not normal astrocytes. DN-ATF5 interferes with CEBPB/CEBPD homodimer and heterodimer formation. Pull-down with mass spectrometry, co-IP, siRNA knockdown, transcriptional reporter assays, cell viability Molecular cancer research : MCR High 31676720
2013 ATF5 5'-UTRα reduces ATF5 mRNA stability by making it a target of nonsense-mediated mRNA decay (NMD): uORF2 translation terminates 125 nt upstream of an exon junction, fulfilling NMD criteria. Knockdown of NMD factors Upf1/Upf2 stabilizes ATF5 mRNA in a uAUG2-dependent manner. Stress-induced eIF2α phosphorylation bypasses uORF2 and stabilizes ATF5 mRNA. Upf1/Upf2 siRNA knockdown, uAUG2 mutagenesis, mRNA stability assays, eIF2α phosphorylation analysis The FEBS journal High 23876217
2012 ATF5 is required for terminal differentiation and survival of olfactory sensory neurons (OSNs): Atf5 knockout mice show massive reduction of mature OSNs due to a differentiation defect and induction of apoptosis. Atf5 is expressed in immature and all mature OSNs, and ectopic Atf5 expression in neural progenitor cells induces OSN-specific gene expression. Atf5 knockout mice, immunostaining with OSN markers, expression profiling, ectopic gene expression Proceedings of the National Academy of Sciences of the United States of America High 23090999
2017 PDX1 directly binds the Atf5 promoter (by ChIP-seq) and regulates ATF5 expression in β-cells. ATF5 is positioned downstream of and parallel to ATF4 in regulating 4EBP1, a mTOR pathway component that inhibits protein translation. ATF5 deficiency attenuates stress suppression of global translation, enhancing β-cell susceptibility to stress-induced apoptosis. ChIP-seq, siRNA knockdown, chromatin occupancy, loss-of-function in β-cell stress models Proceedings of the National Academy of Sciences of the United States of America High 28115692
2019 Pharmacological UPRmt induction is cardioprotective in an ATF5-dependent manner: in vivo UPRmt inducers protect against cardiac ischemia-reperfusion injury in wild-type but not global Atf5-/- mice. RNA-Seq revealed an ATF5-dependent gene set upregulated by UPRmt induction. Atf5 global knockout mice, ex vivo and in vivo ischemia-reperfusion injury model, RNA-Seq, qPCR/Western blot American journal of physiology. Heart and circulatory physiology High 31274354
2014 NLK (Nemo-like kinase) interacts with ATF5 and inhibits its proteasome-dependent degradation in a kinase-independent manner. TAK1, acting upstream of NLK downstream of IL-1β, similarly stabilizes ATF5. NLK and ATF5 cooperate to activate C/EBP, and NLK cannot activate C/EBP upon ATF5 knockdown. Co-IP, NLK/ATF5 overexpression and knockdown, proteasome inhibition, luciferase reporter assay, NLK kinase-dead mutant Molecular and cellular biology High 25512613
2009 ATF5 protein is degraded via the ubiquitin-proteasome pathway; cadmium stabilizes ATF5 protein by interfering with a post-ubiquitination step of proteasomal degradation without reducing ubiquitination of ATF5. The N-terminal region contains a nuclear export signal but is not the ubiquitination site. Ubiquitination assays, proteasome inhibitor comparison, cadmium treatment, N-terminal deletion mutants Biochemical and biophysical research communications Medium 19285020
2013 ATF5 overexpression in adult neurons reduces ER stress-induced apoptosis; ATF5 levels increase in hippocampal neurons upon ER stress (tunicamycin injection or kainate-induced status epilepticus). ATF5 induction occurs preferentially in neuronal fields resistant to apoptosis, suggesting a neuroprotective role. ATF5 overexpression/siRNA in primary neuronal cultures, in vivo status epilepticus model, in situ hybridization, immunohistochemistry Brain : a journal of neurology Medium 23518711
2008 ATF5 is a liver-enriched transcription factor that cooperates with constitutive androstane receptor (CAR) to transactivate CYP2B6; re-expression of ATF5 in HepG2 cells by adenoviral transduction markedly upregulates CYP2B6 mRNA. ATF5 and CYP2B6 are co-induced under ER stress conditions. Adenoviral transduction, qRT-PCR, cotransfection with CAR, ER stress induction Drug metabolism and disposition: the biological fate of chemicals Medium 18332083
2005 ATF5 activates asparagine synthetase (ASNS) promoter transcription via the nutrient-sensing response unit (NSRU) but not via CRE-containing elements. CHOP impairs ATF5-mediated or ATF4-mediated transcriptional activation of the ASNS promoter following amino acid deprivation. Promoter reporter assays (transient transfection), overexpression of ATF5 and CHOP Biological chemistry Medium 16164412
2008 ATF5 suppresses the transactivational activity of p53 and p63 as demonstrated by luciferase reporter assays; ATF5 gene transfer restores radioresistance in a radiosensitive clone that lost ATF5 expression. Luciferase reporter assay for p53/p21, ATF5 gene transfer, microarray, colony assay Cell structure and function Medium 19293535
2017 Human cytomegalovirus immediate-early protein IE86 physically interacts with and acetylates ATF5, promoting glioma cell survival. IE86 staining positively correlates with ATF5 staining in GBM samples. Co-IP, acetylation assay, overexpression, in vitro and in vivo tumor growth assays Oncotarget Medium 28473657
2022 ATF5 is required for mitochondrial quality control in skeletal muscle: ATF5 KO mice show enlarged, less functional mitochondrial pools with enhanced biogenesis (increased PGC-1α), attenuated mitophagy, reduced antioxidant proteins, increased ROS emission, and blunted UPRmt gene expression response to acute exercise. Acute exercise enriches ATF5 in mitochondrial fractions rather than promoting nuclear translocation. ATF5 KO mice, subcellular fractionation, mitochondrial oxygen consumption/ROS assays, exercise protocol, Western blot, qPCR Molecular metabolism High 36332794
2022 ATF5 promotes intestinal barrier function and a satiety response by transcriptionally regulating the gastrointestinal peptide hormone cholecystokinin, which promotes leptin secretion. This mechanism protects against obesity-associated hyperglycemia that is detrimental to barrier function. ATF5 conditional and global knockout mice, enteric pathogen challenge, transcriptional analysis, hormone measurements Cell reports High 36516750
2023 TMEM11 directly interacts with METTL1 and enhances m7G methylation of Atf5 mRNA, increasing ATF5 expression. ATF5 in turn promotes transcription of Inca1 (a CDK inhibitor), suppressing cardiomyocyte proliferation. TMEM11 deletion enhances cardiomyocyte proliferation and cardiac regeneration after injury. Co-IP, m7G MeRIP-seq, ATF5 overexpression, ChIP, siRNA knockdown, in vivo myocardial injury model Cell death and differentiation High 37286744
2012 ATF5 reciprocally interacts with Sonic hedgehog (Shh) signaling in cerebellar granule neuron progenitors (CGNPs): Shh promotes ATF5 expression via a post-transcriptional (protein stabilization) mechanism, and ATF5 in turn promotes Shh-stimulated CGNP proliferation and delays differentiation. Dominant-negative ATF5 diminishes Shh-stimulated CGNP proliferation. Dominant-negative ATF5, constitutive ATF5 expression in CGNPs, Shh treatment, BrdU proliferation assay, protein stability analysis Developmental neurobiology Medium 22095825
2010 The ATF5 promoter was mapped to the region −105 to +3 relative to the transcription start site. EBF1 transcription factor binds to the ATF5 promoter and regulates ATF5 transcription in an EBF-binding-site-independent manner. Promoter deletion analysis, luciferase reporter assay, EBF1 binding analysis Journal of biochemistry Medium 20423929
2013 ATF5 protein is stabilized by IL-1β through its N-terminal hydrophobic amino acids, which serve as both a destabilization domain under steady-state conditions and an IL-1β response domain. IL-1β also increases ATF5 translational efficiency via 5'-UTRα and eIF2α phosphorylation. ATF5 negatively regulates IL-1β-induced SAA1 and SAA2 gene expression. N-terminal deletion/point mutants, protein stability assays, translational efficiency analysis, ATF5 siRNA knockdown, SAA1/SAA2 mRNA measurement The Journal of biological chemistry Medium 24379400
2021 ELF1 transcription factor binds to and activates the ATF5 gene promoter in glioma; ELF1 silencing inhibits glioma cell growth and migration via ATF5. Luciferase assay and ChIP confirm direct ELF1 binding to the ATF5 promoter. Luciferase reporter assay, ChIP, siRNA knockdown, bioinformatics ACS chemical neuroscience Medium 33720698
2019 PRMT1 promotes neuroblastoma cell survival through ATF5: PRMT1 depletion decreases ATF5 expression and induces apoptosis, while ATF5 overexpression rescues apoptosis triggered by PRMT1 inhibition. ATF5 acts as a downstream effector of PRMT1-mediated survival signaling. siRNA/shRNA knockdown, PRMT1 inhibitor treatment, ATF5 overexpression rescue, in vitro and in vivo tumor models Oncogenesis Medium 32415090
2019 Dominant-negative ATF5 rapidly depletes survivin (BIRC5) in tumor cells at both mRNA and protein levels. Survivin protein depletion is driven partly by enhanced proteasomal turnover and depletion of the deubiquitinase USP9X. Survivin loss precedes cell death but survivin overexpression does not rescue DN-ATF5-induced apoptosis, indicating multiple mechanisms. DN-ATF5 vector delivery, qRT-PCR, proteasome inhibitor rescue, USP9X analysis, overexpression rescue Cell death & disease Medium 31551409
2024 METTL14 facilitates m6A modification of ATF5 mRNA, promoting its degradation. ATF5 overexpression reverses METTL14-mediated stemness inhibition in gastric cancer by increasing WDR74 transcription and enhancing β-catenin nuclear translocation. ATF5 directly binds and stimulates the WDR74 promoter as shown by ChIP and luciferase assays. MeRIP assay, luciferase reporter assay, ChIP, siRNA knockdown, Western blot Cancer science Medium 39497511
2024 In obese female mice, suppressed AMPK activity increases the binding affinity of the ATF5-POLG protein complex to mutated mtDNA D-loop and protein-coding regions, promoting replication of heteroplasmic mtDNA and impairing oocyte quality. AMPK activation blocks ATF5-POLG protein recruitment to mutated mtDNA. AMPK knockout mice, single-oocyte mtDNA sequencing, protein-DNA binding assays, AMPK activator treatment Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 38499990
2019 Co-expression of C/EBPγ and ATF5 (but not either alone) increases Vmn2r66 (V2r) promoter reporter activity via the C/EBP:ATF response element (CARE) in Neuro2a cells, suggesting cooperative transcriptional activation in vomeronasal sensory neuron differentiation. Luciferase reporter assay with CARE site, co-transfection of C/EBPγ and ATF5 Cell and tissue research Low 31309319
2021 ATF5 is identified as a transcriptional regulator of Idh2 (isocitrate dehydrogenase-2) in skeletal muscle; AAV-mediated ATF5 overexpression reduced muscle fiber size and MyHC-IIB mRNA while increasing MyHC-IIA and Idh2 mRNA, suggesting fiber-type and metabolic gene regulation. AAV-mediated gene overexpression in mouse tibialis anterior, qRT-PCR, fiber type analysis Scientific reports Low 34611283
2023 ASGR1 promotes monocyte-to-macrophage differentiation via upregulation of ATF5 through NF-κB/IKBa phosphorylation; ASGR1 directly interacts with ATF5 as shown by co-IP. Co-IP, siRNA knockdown/overexpression, Western blot, flow cytometry, in vivo LPS sepsis model Life sciences Medium 36621538

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2016 The Transcription Factor ATF5 Mediates a Mammalian Mitochondrial UPR. Current biology : CB 516 27426517
2008 Phosphorylation of eIF2 directs ATF5 translational control in response to diverse stress conditions. The Journal of biological chemistry 243 18195013
2013 CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis. Molecular biology of the cell 185 23761072
2010 A genome-wide RNA interference screen reveals an essential CREB3L2-ATF5-MCL1 survival pathway in malignant glioma with therapeutic implications. Nature medicine 148 20495567
2011 BCR-ABL suppresses autophagy through ATF5-mediated regulation of mTOR transcription. Blood 119 21715304
2007 Stress-induced translation of ATF5 mRNA is regulated by the 5'-untranslated region. The Journal of biological chemistry 119 18055463
2003 Regulated expression of ATF5 is required for the progression of neural progenitor cells to neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 116 12805299
2019 Cardioprotection by the mitochondrial unfolded protein response requires ATF5. American journal of physiology. Heart and circulatory physiology 109 31274354
2017 Mitochondrial dysfunction in cancer: Potential roles of ATF5 and the mitochondrial UPR. Seminars in cancer biology 93 28499833
2007 The transcription factor ATF5 is widely expressed in carcinomas, and interference with its function selectively kills neoplastic, but not nontransformed, breast cell lines. International journal of cancer 79 17266024
2006 Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5. Oncogene 77 16170340
2011 BCL-2 is a downstream target of ATF5 that mediates the prosurvival function of ATF5 in a cell type-dependent manner. The Journal of biological chemistry 75 21212266
2008 The transcription factor ATF5: role in neurodevelopment and neural tumors. Journal of neurochemistry 73 19046351
2016 A Synthetic Cell-Penetrating Dominant-Negative ATF5 Peptide Exerts Anticancer Activity against a Broad Spectrum of Treatment-Resistant Cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 66 27126996
2005 ATF5 regulates the proliferation and differentiation of oligodendrocytes. Molecular and cellular neurosciences 63 15950153
2017 ATF5 regulates β-cell survival during stress. Proceedings of the National Academy of Sciences of the United States of America 54 28115692
2017 The transcription factor ATF5: role in cellular differentiation, stress responses, and cancer. Oncotarget 54 29137451
2011 HSP70 protein promotes survival of C6 and U87 glioma cells by inhibition of ATF5 degradation. The Journal of biological chemistry 52 21521685
2013 Protective neuronal induction of ATF5 in endoplasmic reticulum stress induced by status epilepticus. Brain : a journal of neurology 51 23518711
2008 ATF5 is a highly abundant liver-enriched transcription factor that cooperates with constitutive androstane receptor in the transactivation of CYP2B6: implications in hepatic stress responses. Drug metabolism and disposition: the biological fate of chemicals 51 18332083
2014 Integrated analyses of DNA methylation and hydroxymethylation reveal tumor suppressive roles of ECM1, ATF5, and EOMES in human hepatocellular carcinoma. Genome biology 49 25517360
2002 Mouse Atf5: molecular cloning of two novel mRNAs, genomic organization, and odorant sensory neuron localization. Genomics 49 12213205
2017 Direct conversion of human fibroblasts into hepatocyte-like cells by ATF5, PROX1, FOXA2, FOXA3, and HNF4A transduction. Scientific reports 48 29192290
2012 Transcription factor ATF5 is required for terminal differentiation and survival of olfactory sensory neurons. Proceedings of the National Academy of Sciences of the United States of America 46 23090999
2011 p300-Dependent ATF5 acetylation is essential for Egr-1 gene activation and cell proliferation and survival. Molecular and cellular biology 46 21791614
2011 ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia. Blood 46 21972289
2005 Regulation of asparagine synthetase gene transcription by the basic region leucine zipper transcription factors ATF5 and CHOP. Biological chemistry 46 16164412
2023 ASGR1 promotes liver injury in sepsis by modulating monocyte-to-macrophage differentiation via NF-κB/ATF5 pathway. Life sciences 45 36621538
2012 Nucleophosmin (NPM1/B23) interacts with activating transcription factor 5 (ATF5) protein and promotes proteasome- and caspase-dependent ATF5 degradation in hepatocellular carcinoma cells. The Journal of biological chemistry 44 22528486
2023 TMEM11 regulates cardiomyocyte proliferation and cardiac repair via METTL1-mediated m7G methylation of ATF5 mRNA. Cell death and differentiation 43 37286744
2019 Dominant-Negative ATF5 Compromises Cancer Cell Survival by Targeting CEBPB and CEBPD. Molecular cancer research : MCR 37 31676720
2012 ATF5 is overexpressed in epithelial ovarian carcinomas and interference with its function increases apoptosis through the downregulation of Bcl-2 in SKOV-3 cells. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 37 23018213
2007 ATF5 promotes cell survival through transcriptional activation of Hsp27 in H9c2 cells. Cell biology international 37 17606386
2006 Amino acid limitation induces expression of ATF5 mRNA at the post-transcriptional level. Life sciences 36 17140605
2015 Hepatic maturation of human iPS cell-derived hepatocyte-like cells by ATF5, c/EBPα, and PROX1 transduction. Biochemical and biophysical research communications 35 26679606
2012 Interference with ATF5 function enhances the sensitivity of human pancreatic cancer cells to paclitaxel-induced apoptosis. Anticancer research 35 23060563
2008 Re-expression of transcription factor ATF5 in hepatocellular carcinoma induces G2-M arrest. Cancer research 35 18701499
2022 ER, Mitochondria, and ISR Regulation by mt-HSP70 and ATF5 upon Procollagen Misfolding in Osteoblasts. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 33 35988140
2020 Novel PGC-1α/ATF5 Axis Partly Activates UPRmt and Mediates Cardioprotective Role of Tetrahydrocurcumin in Pathological Cardiac Hypertrophy. Oxidative medicine and cellular longevity 33 33425220
2015 ATF5 Connects the Pericentriolar Materials to the Proximal End of the Mother Centriole. Cell 33 26213385
2012 The endoplasmic reticulum stress transducer BBF2H7 suppresses apoptosis by activating the ATF5-MCL1 pathway in growth plate cartilage. The Journal of biological chemistry 33 22936798
2013 The 5'-untranslated region regulates ATF5 mRNA stability via nonsense-mediated mRNA decay in response to environmental stress. The FEBS journal 32 23876217
2020 PRMT1 promotes neuroblastoma cell survival through ATF5. Oncogenesis 30 32415090
2011 Regulated ATF5 loss-of-function in adult mice blocks formation and causes regression/eradication of gliomas. Oncogene 30 21725368
2023 ATF5 regulates tubulointerstitial injury in diabetic kidney disease via mitochondrial unfolded protein response. Molecular medicine (Cambridge, Mass.) 29 37095454
2016 Role of ATF5 in the invasive potential of diverse human cancer cell lines. Biochemical and biophysical research communications 29 27125458
2017 Targeting ATF5 in Cancer. Trends in cancer 28 28718401
2010 Regulation of the human CHOP gene promoter by the stress response transcription factor ATF5 via the AARE1 site in human hepatoma HepG2 cells. Life sciences 25 20654631
2018 Expression of activating transcription factor 5 (ATF5) is increased in astrocytomas of different WHO grades and correlates with survival of glioblastoma patients. OncoTargets and therapy 24 30584325
2024 Engineered Exosomes with ATF5-Modified mRNA Loaded in Injectable Thermogels Alleviate Osteoarthritis by Targeting the Mitochondrial Unfolded Protein Response. ACS applied materials & interfaces 23 38626424
2021 ELF1 Transcription Factor Enhances the Progression of Glioma via ATF5 promoter. ACS chemical neuroscience 22 33720698
2019 Propofol Regulates Neural Stem Cell Proliferation and Differentiation via Calmodulin-Dependent Protein Kinase II/AMPK/ATF5 Signaling Axis. Anesthesia and analgesia 22 30303867
2016 Regression/eradication of gliomas in mice by a systemically-deliverable ATF5 dominant-negative peptide. Oncotarget 22 26863637
2008 Cdc34-mediated degradation of ATF5 is blocked by cisplatin. The Journal of biological chemistry 22 18458088
2023 Targeting Transcription Factors ATF5, CEBPB and CEBPD with Cell-Penetrating Peptides to Treat Brain and Other Cancers. Cells 21 36831248
2014 Stabilization of ATF5 by TAK1-Nemo-like kinase critically regulates the interleukin-1β-stimulated C/EBP signaling pathway. Molecular and cellular biology 21 25512613
2012 ATF5, a possible regulator of osteogenic differentiation in human adipose-derived stem cells. Journal of cellular biochemistry 19 22442021
2022 ATF5 is a regulator of exercise-induced mitochondrial quality control in skeletal muscle. Molecular metabolism 18 36332794
2021 ATF5, a putative therapeutic target for the mitochondrial DNA 3243A > G mutation-related disease. Cell death & disease 18 34262025
2019 Dominant-negative ATF5 rapidly depletes survivin in tumor cells. Cell death & disease 18 31551409
2005 ATF5 increases cisplatin-induced apoptosis through up-regulation of cyclin D3 transcription in HeLa cells. Biochemical and biophysical research communications 18 16300731
2024 CTRP3 alleviates mitochondrial dysfunction and oxidative stress injury in pathological cardiac hypertrophy by activating UPRmt via the SIRT1/ATF5 axis. Cell death discovery 17 38278820
2021 Maf1 suppression of ATF5-dependent mitochondrial unfolded protein response contributes to rapamycin-induced radio-sensitivity in lung cancer cell line A549. Aging 17 33640883
2017 Human cytomegalovirus immediate-early protein promotes survival of glioma cells through interacting and acetylating ATF5. Oncotarget 17 28473657
2024 ATF5-Mediated Mitochondrial Unfolded Protein Response (UPRmt) Protects Neurons Against Oxygen-Glucose Deprivation and Cerebral Ischemia. Stroke 16 38913800
2021 ATF5 and HIF1α cooperatively activate HIF1 signaling pathway in esophageal cancer. Cell communication and signaling : CCS 16 33980247
2017 The neuroprotective transcription factor ATF5 is decreased and sequestered into polyglutamine inclusions in Huntington's disease. Acta neuropathologica 16 28861715
2015 Activating transcription factor 5 (ATF5) is essential for the maturation and survival of mouse basal vomeronasal sensory neurons. Cell and tissue research 16 26395637
2007 Association analysis of ATF4 and ATF5, genes for interacting-proteins of DISC1, in bipolar disorder. Neuroscience letters 16 17346882
2024 METTL14 attenuates cancer stemness by suppressing ATF5/WDR74/β-catenin axis in gastric cancer. Cancer science 15 39497511
2023 ATF5 Attenuates the Secretion of Pro-Inflammatory Cytokines in Activated Microglia. International journal of molecular sciences 15 36834738
2009 Cadmium interferes with the degradation of ATF5 via a post-ubiquitination step of the proteasome degradation pathway. Biochemical and biophysical research communications 15 19285020
2022 ATF5 Attenuates Apoptosis in Hippocampal Neurons with Seizures Evoked by Mg2+-Free Medium via Regulating Mitochondrial Unfolded Protein Response. Neurochemical research 14 35939173
2021 Activating transcription factor 5 (ATF5) promotes tumorigenic capability and activates the Wnt/b-catenin pathway in bladder cancer. Cancer cell international 14 34895217
2023 ATF5-regulated Mitochondrial Unfolded Protein Response Attenuates Neuronal Damage in Epileptic Rat by Reducing Endoplasmic Reticulum Stress Through Mitochondrial ROS. Neurochemical research 13 37847329
2022 The mitochondrial UPR regulator ATF5 promotes intestinal barrier function via control of the satiety response. Cell reports 13 36516750
2024 Salvianolic acid B improves mitochondrial dysfunction of septic cardiomyopathy via enhancing ATF5-mediated mitochondrial unfolded protein response. Toxicology and applied pharmacology 12 39153513
2023 ATF5 promotes malignant T cell survival through the PI3K/AKT/mTOR pathway in cutaneous T cell lymphoma. Frontiers in immunology 12 38223508
2018 SUMO2/3 modification of activating transcription factor 5 (ATF5) controls its dynamic translocation at the centrosome. The Journal of biological chemistry 12 29326161
2017 Expression and targeting of transcription factor ATF5 in dog gliomas. Veterinary and comparative oncology 12 28480569
2012 Reciprocal actions of ATF5 and Shh in proliferation of cerebellar granule neuron progenitor cells. Developmental neurobiology 12 22095825
2024 The mitochondrial UPR induced by ATF5 attenuates intervertebral disc degeneration via cooperating with mitophagy. Cell biology and toxicology 11 38472656
2024 AMPK Suppression Due to Obesity Drives Oocyte mtDNA Heteroplasmy via ATF5-POLG Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 11 38499990
2023 ATF5 Attenuates Low-magnesium-induced Apoptosis by Inhibiting Endoplasmic Reticulum Stress Via the Regulation of Mitochondrial Reactive Oxygen Species. Neuroscience 11 37913858
2021 ATF5 deficiency causes abnormal cortical development. Scientific reports 11 33790322
2009 Novel function of transcription factor ATF5: blockade of p53-dependent apoptosis induced by ionizing irradiation. Cell structure and function 11 19293535
2024 GDF-15 Predicts Epithelioid Hemangioendothelioma Aggressiveness and Is Downregulated by Sirolimus through ATF4/ATF5 Suppression. Clinical cancer research : an official journal of the American Association for Cancer Research 10 39283723
2013 N-terminal hydrophobic amino acids of activating transcription factor 5 (ATF5) protein confer interleukin 1β (IL-1β)-induced stabilization. The Journal of biological chemistry 10 24379400
2019 Co-expression of C/EBPγ and ATF5 in mouse vomeronasal sensory neurons during early postnatal development. Cell and tissue research 9 31309319
2010 Identification and characterization of the promoter of human ATF5 gene. Journal of biochemistry 9 20423929
2022 ATF5 is a regulator of ER stress and β-cell apoptosis in different mouse models of genetic- and diet-induced obesity and diabetes mellitus. Cellular signalling 8 36436799
2024 Trimethylamine-N-oxide accelerates osteoporosis by PERK activation of ATF5 unfolding. Cellular and molecular life sciences : CMLS 7 39719538
2020 ATF5 involved in radioresistance in nasopharyngeal carcinoma by promoting epithelial-to-mesenchymal phenotype transition. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery 7 32342199
2023 Activating transcription factor 5 (ATF5) controls intestinal tuft and goblet cell expansion upon succinate-induced type 2 immune responses in mice. Cell and tissue research 6 37256362
2021 Functional validation of epitope-tagged ATF5 knock-in mice generated by improved genome editing of oviductal nucleic acid delivery (i-GONAD). Cell and tissue research 6 33825962
2021 Effect of AAV-mediated overexpression of ATF5 and downstream targets of an integrated stress response in murine skeletal muscle. Scientific reports 6 34611283
2025 Stiff extracellular matrix activates the transcription factor ATF5 to promote the proliferation of cancer cells. iScience 5 40124511
2023 mTORC2 orchestrates monocytic and granulocytic lineage commitment by an ATF5-mediated pathway. iScience 5 37649699
2020 Expression of activating transcription factor 5 (ATF5) is mediated by microRNA-520b-3p under diverse cellular stress in cancer cells. PloS one 5 32603335
2012 Influence of the valine zipper region on the structure and aggregation of the basic leucine zipper (bZIP) domain of activating transcription factor 5 (ATF5). Molecular pharmaceutics 5 23067245