Affinage

ATF5

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

Length
282 aa
Mass
30.7 kDa
Annotated
2026-06-09
100 papers in source corpus 42 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATF5 is a stress-responsive bZIP transcription factor that governs cell survival, organellar proteostasis, and progenitor cell fate, acting as a convergence point between translational stress signaling and transcriptional cell-fate decisions (PMID:18195013, PMID:18055463, PMID:12805299, PMID:27426517). Its expression is controlled predominantly at the level of translation: the 5'-UTRα of ATF5 mRNA contains an inhibitory uORF2 that represses basal translation, and eIF2α phosphorylation during amino acid deprivation, ER stress, or oxidative stress causes ribosomes to bypass uORF2 and translate the coding region, a regulatory logic analogous to ATF4 (PMID:18195013, PMID:18055463). The same uORF2-dependent translation event renders the transcript a substrate of nonsense-mediated decay under basal conditions, so eIF2α phosphorylation simultaneously stabilizes the mRNA, coupling translational and decay control (PMID:23876217). ATF5 transcription is itself driven by stress effectors including CHOP and ATF4, the ER-stress transducer BBF2H7, and lineage factors such as PDX1, forming feed-forward loops that amplify the stress response (PMID:23761072, PMID:22936798, PMID:28115692). Protein abundance is set by ubiquitin-proteasome degradation initiated through N-terminal ubiquitination and the E2 enzyme Cdc34, antagonized by HSP70 binding to the N-terminal activation domain and promoted by nucleophosmin (NPM1), which displaces HSP70; NLK and stress signals further stabilize the protein (PMID:18458088, PMID:21521685, PMID:22528486, PMID:25512613). As a transcription factor ATF5 drives a prosurvival program, directly activating anti-apoptotic targets MCL1 and BCL-2 in cancer cells, mTOR, Hsp27, and ASNS, and its activity is enhanced by p300-mediated acetylation at K29 (PMID:20495567, PMID:21212266, PMID:21715304, PMID:21791614, PMID:16164412). ATF5 mediates the mitochondrial unfolded protein response, partitioning between mitochondria and nucleus so that during organellar stress a fraction traffics to the nucleus to induce a proteostasis-restoring gene set, a function required for cardioprotection and skeletal-muscle mitochondrial quality control in vivo (PMID:27426517, PMID:31274354, PMID:36332794). Beyond its transcriptional role, ATF5 is a structural component of the centrosome, forming a 9-fold symmetric ring that links polyglutamylated tubulin on the mother centriole to PCNT in the pericentriolar material, with its centrosomal residence gated by cell-cycle-dependent SUMO2/3 modification (PMID:26213385, PMID:29326161). In development, ATF5 maintains neural and oligodendrocyte progenitors in an undifferentiated state and is required for terminal differentiation and survival of olfactory sensory neurons, where it directly regulates targets including Rtp1 and cooperates with C/EBP family partners (PMID:12805299, PMID:15950153, PMID:23090999, PMID:33825962, PMID:31309319).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2003 High

    Established ATF5 as a brake on neural progenitor differentiation, defining its first developmental role and showing it acts through repression of CRE-dependent transcription.

    Evidence Gain-of-function, dominant-negative, and siRNA manipulation with NGF treatment and CRE reporters in PC12 and telencephalic cells

    PMID:12805299

    Open questions at the time
    • Direct in vivo target genes not identified
    • Mechanism of CRE repression unresolved
  2. 2007 High

    Defined how ATF5 abundance is tuned to stress, showing alternative 5'-UTRs and an inhibitory uORF2 confer eIF2α-phosphorylation-dependent translational induction.

    Evidence Reporter assays with 5'-UTR variants and uORF mutations plus eIF2α phosphorylation analysis

    PMID:18055463

    Open questions at the time
    • Did not address mRNA stability layer
    • Endogenous protein induction quantified only indirectly
  3. 2008 High

    Resolved the uORF reinitiation logic mechanistically and linked basal expression to ATF4, placing ATF5 in an integrated stress response cascade.

    Evidence Polyribosome fractionation, uORF mutant reporters, ATF4-/- MEFs, and pharmacological eIF2 kinase activation

    PMID:18055463 PMID:18195013

    Open questions at the time
    • Quantitative contribution of transcriptional vs translational control in vivo unclear
  4. 2008 Medium

    Identified the degradation arm of ATF5 control, showing proteasomal turnover via N-terminal ubiquitination and the E2 enzyme Cdc34.

    Evidence Ubiquitination assays, N-terminal methionine mutants, Cdc34 Co-IP, and cisplatin treatment

    PMID:18458088

    Open questions at the time
    • E3 ligase not identified
    • N-terminal ubiquitination inferred from deletion mutants
    • Single lab
  5. 2010 High

    Demonstrated that oncogenic signaling drives ATF5 to enforce cancer cell survival via direct anti-apoptotic transcription, identifying MCL1 as a key target.

    Evidence Genome-wide RNAi screen, ChIP, and reporter assays in glioma samples and mouse models

    PMID:20495567

    Open questions at the time
    • Generality of CREB3L2-ATF5 axis beyond glioma untested
    • Other survival targets not enumerated here
  6. 2011 High

    Defined ATF5's prosurvival transcriptional program in detail — direct BCL-2 and mTOR activation — and revealed cancer-cell-specific target regulation.

    Evidence ChIP, EMSA, reporter assays, knockdown/rescue in glioma, breast cancer, and BCR-ABL cells

    PMID:21212266 PMID:21715304

    Open questions at the time
    • Basis of cancer-cell-specific BCL-2 regulation not molecularly resolved
    • In vivo target occupancy not shown
  7. 2011 High

    Established post-translational control of ATF5 stability and activity, showing HSP70 binding protects it from degradation and p300 acetylation at K29 boosts its transcriptional output.

    Evidence Reciprocal Co-IP, ATP-dependence and domain mapping, in vitro acetylation, K29 mutagenesis, and ChIP

    PMID:21521685 PMID:21791614

    Open questions at the time
    • Stoichiometry and dynamics of HSP70/acetylation in vivo unclear
    • Deacetylase not identified
  8. 2012 High

    Identified NPM1 as a destabilizer that antagonizes HSP70, and demonstrated ATF5's requirement for olfactory sensory neuron maturation in vivo, unifying its survival and differentiation roles.

    Evidence TAP-MS, Co-IP and domain mapping for NPM1; Atf5-/- mice with OSN markers and ectopic expression

    PMID:22528486 PMID:23090999

    Open questions at the time
    • NPM1/HSP70 competition not reconstituted in vitro
    • Direct OSN target genes not defined in this work
  9. 2013 High

    Showed ATF5 can act as a pro-apoptotic effector during severe stress and is a substrate of NMD, integrating decay control with the eIF2α translational switch.

    Evidence ChIP, transcriptome profiling, NMD factor (Upf1/Upf2) knockdown, and mRNA stability assays under stress

    PMID:23761072 PMID:23876217

    Open questions at the time
    • Determinants of pro-survival vs pro-apoptotic ATF5 outputs unresolved
    • NOXA induction mechanism not detailed
  10. 2015 High

    Revealed an unexpected non-transcriptional role: ATF5 is a structural centrosomal protein bridging the mother centriole to the pericentriolar material, required for genome stability.

    Evidence Super-resolution microscopy showing 9-fold symmetry, Co-IP with polyglutamylated tubulin and PCNT, and RNAi depletion phenotypes

    PMID:26213385

    Open questions at the time
    • How the bZIP transcription factor is repurposed structurally unknown
    • Relationship between centrosomal and nuclear pools unclear
  11. 2016 High

    Defined ATF5 as the mammalian UPRmt regulator, functionally orthologous to C. elegans ATFS-1, governed by mitochondria-to-nucleus partitioning.

    Evidence Cellular fractionation, cross-species genetic rescue in atfs-1 worms, mammalian siRNA, and reporter assays

    PMID:27426517

    Open questions at the time
    • Molecular sensor controlling mitochondrial import vs nuclear trafficking not defined
    • Full UPRmt target set incomplete
  12. 2018 High

    Showed SUMO2/3 modification cyclically gates ATF5's centrosomal residence across the cell cycle, coupling its post-translational state to the centrosome cycle.

    Evidence SUMO modification assays, cell-cycle synchronization, SUMO-site mutant, and Co-IP with centrosomal proteins

    PMID:29326161

    Open questions at the time
    • SUMO E3 ligase and protease not identified
    • Crosstalk with the transcriptional/UPRmt roles unexplored
  13. 2019 High

    Validated ATF5's UPRmt and survival functions physiologically, demonstrating it is required for cardioprotection in vivo, and mapped its interface with the C/EBP family.

    Evidence Atf5-/- mice with ischemia-reperfusion and RNA-Seq; pull-down/MS identifying CEBPB, CEBPD, CCDC6 with functional knockdown

    PMID:31274354 PMID:31676720

    Open questions at the time
    • Identity of ATF5 dimerization partners in each context not fully resolved
    • Cardioprotective gene set not mechanistically dissected
  14. 2023 High

    Extended ATF5 regulation to RNA modification, showing m7G methylation of Atf5 mRNA controls its expression to restrain cardiomyocyte proliferation.

    Evidence Co-IP (TMEM11-METTL1), m7G-MeRIP-seq, ChIP for ATF5 at the Inca1 promoter, and a mouse myocardial injury model

    PMID:37286744

    Open questions at the time
    • Direct effect of m7G on ATF5 translation vs stability not separated
    • Generality beyond cardiac context untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ATF5 partitions among its mitochondrial, centrosomal, and nuclear pools, and what molecular switch selects between its prosurvival and pro-apoptotic transcriptional outputs, remain unresolved.
  • No structural model linking bZIP and centrosomal functions
  • Sensor controlling mitochondrial import vs nuclear trafficking unknown
  • Determinants of survival vs death transcriptional programs undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11 GO:0003677 DNA binding 5 GO:0005198 structural molecule activity 1 GO:0060090 molecular adaptor activity 1
Localization
GO:0005634 nucleus 3 GO:0005739 mitochondrion 3 GO:0005815 microtubule organizing center 2
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-392499 Metabolism of proteins 6 R-HSA-8953897 Cellular responses to stimuli 6 R-HSA-1266738 Developmental Biology 5 R-HSA-5357801 Programmed Cell Death 5 R-HSA-1640170 Cell Cycle 4 R-HSA-1852241 Organelle biogenesis and maintenance 3
Partners
CDC34CEBPBCEBPDHSP70NLKNPM1PCNTPOLG
Complex memberships
centrosome/pericentriolar material ring

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 ATF5 is a mammalian transcription factor that mediates the mitochondrial unfolded protein response (UPRmt). Like C. elegans ATFS-1, ATF5 is regulated by organelle partitioning: it normally accumulates in mitochondria, but during mitochondrial stress a fraction traffics to the nucleus to activate UPRmt target genes. ATF5 expression rescues UPRmt signaling in atfs-1-deficient worms requiring the same UPRmt promoter element identified in C. elegans, and mammalian cells require ATF5 to maintain mitochondrial activity during stress. Cellular fractionation, ATF5 expression in atfs-1-deficient C. elegans (genetic complementation), siRNA knockdown in mammalian cells, reporter assays Current Biology High 27426517
2008 ATF5 translation is preferentially induced during stress by a mechanism requiring eIF2α phosphorylation. The 5'-leader of ATF5 mRNA contains two uORFs analogous to ATF4: uORF1 is positive-acting (allows reinitiation), and uORF2 is inhibitory under normal conditions. eIF2α phosphorylation during stress delays reinitiation, causing ribosomes to bypass uORF2 and instead translate the ATF5 coding region. Additionally, ATF4 contributes to basal ATF5 transcription. Polyribosome fractionation, luciferase reporter assays with uORF mutations, ATF4-/- mouse embryo fibroblasts, pharmacological eIF2 kinase activation Journal of Biological Chemistry High 18055463 18195013
2007 ATF5 mRNA translation is regulated by alternative 5'-UTRs (5'-UTRα and 5'-UTRβ). 5'-UTRα represses basal translation via uORF2, but this repression is released by amino acid limitation or arsenite exposure through eIF2α phosphorylation. 5'-UTRβ does not confer stress-responsive translational upregulation. Mutation of uAUG2 in uORF2 restored basal expression and abolished stress-induced upregulation. Reporter assays with 5'-UTR variants and uORF mutations, eIF2α phosphorylation analysis, heme-regulated inhibitor kinase overexpression Journal of Biological Chemistry High 18055463
2013 CHOP directly induces ATF5 transcription as part of a feedforward apoptotic switch during severe proteotoxic stress. ATF4 also directly activates ATF5 transcription. Knockdown of ATF5 increases cell survival during proteasome inhibition. ATF5-dependent transcriptome analysis identified NOXA as an ATF5 target important for cell death. Chromatin immunoprecipitation, ATF5 knockdown (siRNA), transcriptome profiling, proteasome inhibitor treatment, cell viability assays Molecular Biology of the Cell High 23761072
2013 The 5'-UTRα of ATF5 mRNA renders it a target of nonsense-mediated mRNA decay (NMD) under normal conditions via translation of uORF2. Knockdown of NMD factors Upf1 and Upf2 stabilized ATF5 mRNA. During amino acid limitation or tunicamycin-induced stress, eIF2α phosphorylation stabilizes ATF5 mRNA by preventing uORF2 translation, thereby linking translational control to mRNA decay regulation. siRNA knockdown of Upf1/Upf2, uORF2 mutation, mRNA stability assays, stress treatment The FEBS Journal High 23876217
2003 ATF5 suppresses neuroprogenitor cell differentiation into neurons. ATF5 is highly expressed in neural stem/progenitor cells and downregulated by NGF. Exogenous ATF5 suppresses NGF-promoted neurite outgrowth and neurogenesis; dominant-negative ATF5 or siRNA accelerates neurogenesis. The inhibitory effect requires repression of CRE sites. Overexpression and dominant-negative ATF5 in PC12 and telencephalic cells, siRNA knockdown, NGF treatment, neurosphere cultures, CRE luciferase reporter Journal of Neuroscience High 12805299
2010 In malignant glioma, RAS-MAPK or PI3K signaling activates CREB3L2, which directly activates ATF5 transcription. ATF5 in turn promotes survival by directly stimulating transcription of the anti-apoptotic gene MCL1. The RAF inhibitor sorafenib suppresses ATF5 expression in glioma stem cells. Genome-wide RNAi screen, ChIP, reporter assays, gene expression analysis in human glioma samples and mouse models Nature Medicine High 20495567
2011 BCR-ABL suppresses autophagy through the PI3K/AKT/FOXO4 pathway, which transcriptionally upregulates ATF5; ATF5 in turn directly stimulates transcription of mTOR, a master negative regulator of autophagy. Imatinib-induced autophagy is caused by inhibition of this BCR-ABL/PI3K/AKT/FOXO4/ATF5/mTOR pathway. Reporter assays, ChIP, ATF5 knockdown, mTOR expression analysis, autophagy assays in BCR-ABL-transformed cells Blood High 21715304
2011 BCL-2 is a direct transcriptional target of ATF5 that mediates its prosurvival function in glioma and breast cancer cells. ATF5 binds to an ATF5-specific regulatory element downstream of and adjacent to the negative regulatory element in the BCL-2 P2 promoter. BCL-2 expression is not regulated by ATF5 in non-transformed cells, explaining the cancer cell-specific survival function. ChIP, EMSA, ATF5 overexpression/knockdown, BCL-2 promoter reporter assays, rescue experiments in multiple cell types Journal of Biological Chemistry High 21212266
2011 HSP70 interacts with the N-terminal activation domain of ATF5 (which is rich in proline residues) through an ATP-driven process requiring functional ATPase on HSP70. HSP70 binding stabilizes ATF5 protein, which is otherwise subject to rapid proteasome-dependent and caspase-dependent degradation. HSP70 depletion accelerates ATF5 degradation and reduces BCL-2 and EGR-1 expression in glioma cells. Co-immunoprecipitation, HSP70 overexpression/siRNA knockdown, ATF5 stability assays, proteasome/caspase inhibitors, domain mapping Journal of Biological Chemistry High 21521685
2011 p300 acetylates ATF5 at lysine-29 (K29), which enhances the ATF5-p300 interaction and binding of the ATF5/p300 complex to the ATF5 response element (ARE) of the EGR-1 promoter. ARE-bound ATF5/p300 then acetylates histone H3 K14 at both ARE and SRE of EGR-1 promoter, facilitating ERK-phosphorylated Elk-1 binding to the SRE and activating EGR-1 transcription. Co-IP, in vitro acetylation assays, ChIP, acetylation-site mutagenesis (K29), promoter reporter assays, ERK inhibition Molecular and Cellular Biology High 21791614
2008 ATF5 protein is degraded via the ubiquitin-proteasome pathway through N-terminal ubiquitinylation of the free amino group of the N-terminal methionine. The E2 ubiquitin-conjugating enzyme Cdc34 is involved in ATF5 ubiquitination. Cisplatin blocks ATF5 degradation by promoting nucleus-to-cytoplasm translocation of Cdc34, reducing ATF5-Cdc34 interaction. Ubiquitination assays, N-terminal methionine mutants, Cdc34 overexpression/co-IP, cisplatin treatment, proteasome inhibitor studies Journal of Biological Chemistry Medium 18458088
2009 Cadmium interferes with ATF5 degradation at a post-ubiquitination step of the proteasome pathway. Unlike proteasome inhibitors (which increase ubiquitinated ATF5), cadmium does not reduce ATF5 ubiquitination but instead blocks a downstream step in proteasomal degradation, stabilizing ATF5 protein. Ubiquitination assays, CdCl2/NaAsO3 treatment, proteasome inhibitor comparison, transient transfection of FLAG-ATF5 Biochemical and Biophysical Research Communications Medium 19285020
2012 Nucleophosmin (NPM1/B23) interacts with ATF5 via the ATF5 leucine zipper domain binding to the C-terminal nucleolar localization signal region of NPM1. NPM1 promotes ATF5 degradation through proteasome-dependent and caspase-dependent pathways. NPM1 interaction displaces HSP70 from ATF5 complexes, antagonizing HSP70-mediated ATF5 stabilization. NPM1-c, a mutant defective in nucleolar localization, failed to stimulate ATF5 polyubiquitination. Tandem affinity purification followed by mass spectrometry, Co-IP, domain mapping, ubiquitination assays, NPM1-c mutant Journal of Biological Chemistry High 22528486
2015 ATF5 forms a characteristic 9-fold symmetrical ring structure in the inner layer of the pericentriolar material (PCM) at the proximal end of the mother centriole. ATF5 interacts with polyglutamylated tubulin (PGT) on the mother centriole and with PCNT in the PCM, functioning as a structural linker required for mother centriole-directed PCM accumulation and PCM-dependent centriole formation. ATF5 depletion causes PCM fragmentation, multi-polar mitotic spindles, and genomic instability. Super-resolution microscopy (9-fold symmetry), Co-IP with PGT and PCNT, ATF5 depletion/RNAi, centrosome fractionation, cell cycle analysis Cell High 26213385
2018 ATF5 is SUMO2/3-modified at a conserved SUMO-targeting consensus site. SUMOylation of ATF5 is elevated in G1 phase and diminished in G2/M phase. SUMOylation disrupts ATF5 interaction with centrosomal proteins, dislodging ATF5 from the centrosome at the end of M phase. Blockade of ATF5 SUMOylation deregulates the centrosome cycle, impedes ATF5 translocation from the centrosome, and causes genomic instability and G2/M arrest. SUMO modification assays, cell-cycle-synchronized cells, SUMOylation-site mutant ATF5, Co-IP with centrosomal proteins, genomic instability assays Journal of Biological Chemistry High 29326161
2012 ATF5 is required for terminal differentiation and survival of olfactory sensory neurons (OSNs). In Atf5-/- mice, OSNs fail to differentiate from immature to mature OSNs and undergo apoptosis, leading to neonatal lethality from olfactory defect. Ectopic ATF5 expression in neural progenitor cells induces expression of multiple OSN-specific genes. Atf5 knockout mice, immunostaining with OSN-specific markers, expression profiling, ectopic ATF5 expression PNAS High 23090999
2005 ATF5 promotes oligodendrocyte progenitor expansion and inhibits their differentiation into mature oligodendroglia. Constitutively expressed ATF5 maintains SVZ cells and O4+ precursors in cycle; ATF5 loss-of-function (dominant-negative) accelerates oligodendrocyte differentiation in vitro and in vivo, but results in aberrant migration. Dominant-negative ATF5 in vitro and in vivo (SVZ cells), constitutive ATF5 expression, BrdU labeling, immunostaining Molecular and Cellular Neurosciences High 15950153
2019 Cardioprotection by pharmacological UPRmt induction (oligomycin or doxycycline) requires ATF5 in vivo. In global Atf5-/- mice, UPRmt induction fails to protect against cardiac ischemia-reperfusion injury, whereas it does in wild-type mice. RNA-Seq revealed an ATF5-dependent gene set induced by UPRmt. Atf5-/- mice, in vivo UPRmt induction, ex vivo ischemia-reperfusion, cardiac qPCR/western blot, RNA-Seq American Journal of Physiology: Heart and Circulatory Physiology High 31274354
2014 Nemo-like kinase (NLK) interacts with ATF5 and inhibits proteasome-dependent degradation of ATF5 in a kinase-independent manner, thereby stabilizing ATF5 protein. NLK cooperates with ATF5 to activate C/EBP transcription. TAK1, upstream of NLK in the IL-1β pathway, mimics NLK's ability to stabilize ATF5 and activate C/EBP, establishing a TAK1-NLK-ATF5-C/EBP signaling axis. Co-IP, luciferase reporter for C/EBP activity, NLK overexpression/knockdown/knockout, ATF5 stability assays, kinase-dead NLK mutant Molecular and Cellular Biology High 25512613
2012 The ER stress transducer BBF2H7 transcriptionally activates ATF5 in chondrocytes. ATF5 in turn activates transcription of Mcl1 to suppress ER stress-induced apoptosis in chondrocytes. This BBF2H7-ATF5-MCL1 pathway is specifically activated during chondrogenesis and is required to counteract ER stress from abundant ECM protein synthesis. Bbf2h7-/- mice, TUNEL staining, ChIP/reporter assays, ATF5 and MCL1 expression analysis in chondrocytes Journal of Biological Chemistry High 22936798
2017 ATF5 is a transcriptional target of PDX1 in pancreatic β-cells (PDX1 binding confirmed by ChIP-sequencing). ATF5 regulates β-cell survival under stress and is positioned downstream of and parallel to ATF4 in the regulation of 4EBP1, a mTOR pathway component that inhibits protein translation. ATF5 deficiency attenuates stress-induced suppression of global translation, increasing β-cell susceptibility to apoptosis. Primary islet ChIP-sequencing for PDX1, ATF5 loss-of-function, 4EBP1 reporter/expression, translation assays PNAS High 28115692
2008 ATF5 is a liver-enriched transcription factor that cooperates with constitutive androstane receptor (CAR) to transactivate CYP2B6. Adenoviral ATF5 overexpression in HepG2 cells selectively upregulates CYP2B6 mRNA, and ATF5+CAR co-expression causes additive CYP2B6 induction. Under ER stress (amino acid limitation), ATF5 is post-transcriptionally upregulated with parallel CYP2B6 induction. Adenoviral transduction, co-transfection with CAR, qRT-PCR, primary human hepatocyte cultures Drug Metabolism and Disposition Medium 18332083
2005 ATF5 activates asparagine synthetase (ASNS) promoter transcription via the nutrient-sensing response unit (NSRU). This transactivation is blocked by CHOP, which acts as a shut-off device for nutrient deprivation-induced ATF5-mediated gene transcription. ATF5 does not transactivate CRE-containing reporter genes. Reporter gene assays with ASNS promoter, ATF5 and CHOP overexpression, deletion/mutation analysis of NSRU Biological Chemistry Medium 16164412
2009 ATF5 suppresses the transactivational activity of p53 and p63 in a luciferase reporter assay. ATF5 overexpression in radiosensitive tumor cells confers resistance to ionizing radiation and Ad-p53-induced apoptosis. Luciferase reporter assay for p53/p63 transactivation, ATF5 gene transfer, colony assay, flow cytometry Cell Structure and Function Medium 19293535
2010 ATF5 directly binds the ID1 gene promoter (demonstrated by EMSA) and represses ID1 transcription in hepatocellular carcinoma cells. Restoration of ATF5 in HCC cells causes G2/M cell cycle arrest. EMSA, reporter assays, flow cytometry cell cycle analysis, ATF5 re-expression in HCC cell lines Cancer Research Medium 18701499
2007 ATF5 promotes cell survival against heat shock in H9c2 cells by transcriptionally activating Hsp27. The CRE motif in the Hsp27 gene promoter is important for ATF5-mediated upregulation, and Hsp27 knockdown by RNAi increases cell death in ATF5-expressing cells. ATF5 overexpression, Hsp27 promoter reporter assays, siRNA knockdown of Hsp27, heat shock survival assay Cell Biology International Medium 17606386
2010 ATF5 activates the CHOP gene promoter via the amino acid response element 1 (AARE1) site in HepG2 cells. ATF5 knockdown reduces arsenite-induced CHOP protein expression and arsenite-induced cell death. Reporter gene assays with CHOP promoter deletions and AARE1 point mutations, ATF5 overexpression, siRNA knockdown Life Sciences Medium 20654631
2019 Dominant-negative ATF5 (DN-ATF5) associates with CEBPB and CEBPD (basic leucine zipper proteins) and coiled-coil protein CCDC6, as identified by unbiased pull-down assays coupled with mass spectrometry. DN-ATF5 interferes with CEBPB and CEBPD transcriptional activity; knockdown of CEBPB or CEBPD promotes apoptosis of cancer cells but not normal astrocytes. Cancer cell death by DN-ATF5 occurs partly through suppression of CEBPB/CEBPD function independent of ATF5 itself. Pull-down assay followed by mass spectrometry, immunoblotting, CEBPB/CEBPD knockdown, reporter assays for CEBPB/CEBPD transcriptional activity Molecular Cancer Research High 31676720
2017 HCMV immediate-early protein IE86 physically interacts with ATF5 and acetylates ATF5, thereby promoting glioma cell survival. Co-IP, immunohistochemistry, ATF5 acetylation assays, IE86 overexpression, glioma xenograft Oncotarget Medium 28473657
2013 ASGR1 interacts with ATF5 (confirmed by Co-IP) and promotes ATF5 expression through NF-κB/IKBa phosphorylation, which in turn promotes monocyte-to-macrophage differentiation. Co-IP, ASGR1 knockdown/overexpression, western blot for NF-κB phosphorylation and ATF5 expression, THP-1 and bone marrow-derived macrophage models Life Sciences Medium 36621538
2023 TMEM11 directly interacts with METTL1 and enhances m7G methylation of Atf5 mRNA, thereby increasing ATF5 expression. Increased ATF5 then promotes transcription of Inca1 (an inhibitor of CDK-cyclin A1), suppressing cardiomyocyte proliferation. TMEM11 deletion enhances cardiomyocyte proliferation and cardiac regeneration. Co-IP (TMEM11-METTL1 interaction), m7G-MeRIP sequencing, ATF5 overexpression/knockdown, ChIP for ATF5 at Inca1 promoter, cardiomyocyte proliferation assays, mouse myocardial injury model Cell Death and Differentiation High 37286744
2022 In skeletal muscle, ATF5 is required for proper mitochondrial quality control. ATF5 KO mice exhibit a larger but less functional mitochondrial pool, with enhanced biogenesis (increased PGC-1α), attenuated mitophagy, reduced antioxidant proteins, and increased ROS emission. Acute exercise causes ATF5 enrichment in mitochondrial fractions rather than nuclear translocation, and loss of ATF5 blunts the mitophagic and UPRmt gene expression response to exercise. ATF5 KO mice, fractionation (nuclear/cytosolic/mitochondrial), oxygen consumption, ROS emission, mRNA analysis, exercise challenge Molecular Metabolism High 36332794
2020 PRMT1 promotes neuroblastoma cell survival through ATF5 as a downstream effector. Overexpression of ATF5 rescues cell apoptosis triggered by PRMT1 inhibition genetically or pharmacologically, placing ATF5 downstream of PRMT1 in a prosurvival signaling pathway. PRMT1 depletion (siRNA/pharmacological), ATF5 overexpression rescue, apoptosis assays, sphere formation assays, in vivo xenograft Oncogenesis Medium 32415090
2024 METTL14 facilitates m6A modification of ATF5 mRNA, promoting its degradation. ATF5 overexpression (caused by METTL14 knockdown) increases WDR74 transcription and enhances β-catenin nuclear translocation, promoting cancer stemness in gastric cancer. Histone H3 lactylation at Lys18 upregulates METTL14 expression. m6A RNA immunoprecipitation (MeRIP), luciferase reporter assays, ChIP (ATF5 binding to WDR74 promoter), western blot for β-catenin, rescue experiments Cancer Science Medium 39497511
2021 ELF1 transcription factor directly binds and activates the ATF5 gene promoter in glioma cells, as confirmed by luciferase reporter assay and chromatin immunoprecipitation (ChIP). Silencing ELF1 inhibits glioma cell growth and migration with ATF5 involvement. Luciferase reporter assays, ChIP, ELF1 siRNA knockdown, cell proliferation and migration assays ACS Chemical Neuroscience Medium 33720698
2024 In oocytes, AMPK suppression (by obesity) increases the binding affinity of the ATF5-POLG protein complex to mutated mtDNA D-loop and protein-coding regions, promoting replication of heteroplasmic mtDNA. AMPK activation prevents ATF5-POLG recruitment to mutated mtDNA, improving oocyte mitochondrial quality. Co-IP (ATF5-POLG interaction), AMPK knockout mice, mtDNA heteroplasmy sequencing, AMPK activator treatment, oocyte maturation assays Advanced Science Medium 38499990
2021 ATF5 directly binds and stimulates the promoter of DVL1 gene (Wnt pathway component) in bladder cancer cells, activating the Wnt/β-catenin pathway. ATF5 promotes tumor sphere formation and cancer stemness through this mechanism. ChIP-qPCR, luciferase reporter assays, ATF5 overexpression/knockdown, sphere formation assays Cancer Cell International Medium 34895217
2019 C/EBPγ and ATF5 co-expression (but not either alone) increases Vmn2r66 promoter reporter activity via the C/EBP:ATF response element (CARE), suggesting ATF5 and C/EBPγ act cooperatively as a heterodimer to drive V2r-type vomeronasal sensory neuron differentiation. Luciferase reporter assays in Neuro2a cells, co-expression experiments with C/EBPγ and ATF5, immunostaining in vomeronasal organ Cell and Tissue Research Medium 31309319
2013 IL-1β increases ATF5 protein expression in HepG2 cells by two mechanisms: stabilization of ATF5 protein via its N-terminal hydrophobic domain, and increased translational efficiency via 5'-UTRα and eIF2α phosphorylation. ATF5 knockdown upregulates IL-1β-induced SAA1 and SAA2 expression, identifying ATF5 as a negative regulator of acute-phase gene expression. N-terminal deletion mutants, protein stability assays, 5'-UTR reporter assays, ATF5 siRNA knockdown, SAA1/2 expression analysis Journal of Biological Chemistry Medium 24379400
2021 ATF5 directly binds the CCAAT/enhancer-binding protein (C/EBP)-ATF response element (CARE) in the promoter region of the olfactory chaperone gene Rtp1, as demonstrated by ChIP in ATF5-HA knock-in mice. This establishes Rtp1 as a direct in vivo transcriptional target of ATF5 in olfactory sensory neurons. CRISPR/Cas9 HA-tag knock-in mice, ChIP with anti-HA antibody, in vivo olfactory epithelium analysis Cell and Tissue Research High 33825962
2022 Intestinal ATF5 promotes a satiety response by transcriptionally regulating the gastrointestinal peptide hormone cholecystokinin (CCK), which promotes leptin secretion, thereby maintaining intestinal barrier function and preventing obesity-associated hyperglycemia and barrier dysfunction during enteric pathogen infection. Atf5-/- mice, intestinal barrier assays, enteric infection models, CCK reporter/expression analysis, leptin measurements Cell Reports Medium 36516750

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 539 27426517
2008 Phosphorylation of eIF2 directs ATF5 translational control in response to diverse stress conditions. The Journal of biological chemistry 248 18195013
2013 CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis. Molecular biology of the cell 193 23761072
2010 A genome-wide RNA interference screen reveals an essential CREB3L2-ATF5-MCL1 survival pathway in malignant glioma with therapeutic implications. Nature medicine 151 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 115 31274354
2017 Mitochondrial dysfunction in cancer: Potential roles of ATF5 and the mitochondrial UPR. Seminars in cancer biology 95 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
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 77 21212266
2006 Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5. Oncogene 77 16170340
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 67 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 53 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
2023 ASGR1 promotes liver injury in sepsis by modulating monocyte-to-macrophage differentiation via NF-κB/ATF5 pathway. Life sciences 47 36621538
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 47 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 TMEM11 regulates cardiomyocyte proliferation and cardiac repair via METTL1-mediated m7G methylation of ATF5 mRNA. Cell death and differentiation 44 37286744
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
2019 Dominant-Negative ATF5 Compromises Cancer Cell Survival by Targeting CEBPB and CEBPD. Molecular cancer research : MCR 38 31676720
2020 Novel PGC-1α/ATF5 Axis Partly Activates UPRmt and Mediates Cardioprotective Role of Tetrahydrocurcumin in Pathological Cardiac Hypertrophy. Oxidative medicine and cellular longevity 37 33425220
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
2022 ER, Mitochondria, and ISR Regulation by mt-HSP70 and ATF5 upon Procollagen Misfolding in Osteoblasts. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 35 35988140
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
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
2023 ATF5 regulates tubulointerstitial injury in diabetic kidney disease via mitochondrial unfolded protein response. Molecular medicine (Cambridge, Mass.) 31 37095454
2020 PRMT1 promotes neuroblastoma cell survival through ATF5. Oncogenesis 30 32415090
2017 Targeting ATF5 in Cancer. Trends in cancer 30 28718401
2011 Regulated ATF5 loss-of-function in adult mice blocks formation and causes regression/eradication of gliomas. Oncogene 30 21725368
2016 Role of ATF5 in the invasive potential of diverse human cancer cell lines. Biochemical and biophysical research communications 29 27125458
2024 Engineered Exosomes with ATF5-Modified mRNA Loaded in Injectable Thermogels Alleviate Osteoarthritis by Targeting the Mitochondrial Unfolded Protein Response. ACS applied materials & interfaces 28 38626424
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 26 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
2016 Regression/eradication of gliomas in mice by a systemically-deliverable ATF5 dominant-negative peptide. Oncotarget 24 26863637
2023 Targeting Transcription Factors ATF5, CEBPB and CEBPD with Cell-Penetrating Peptides to Treat Brain and Other Cancers. Cells 23 36831248
2019 Propofol Regulates Neural Stem Cell Proliferation and Differentiation via Calmodulin-Dependent Protein Kinase II/AMPK/ATF5 Signaling Axis. Anesthesia and analgesia 23 30303867
2021 ELF1 Transcription Factor Enhances the Progression of Glioma via ATF5 promoter. ACS chemical neuroscience 22 33720698
2014 Stabilization of ATF5 by TAK1-Nemo-like kinase critically regulates the interleukin-1β-stimulated C/EBP signaling pathway. Molecular and cellular biology 22 25512613
2008 Cdc34-mediated degradation of ATF5 is blocked by cisplatin. The Journal of biological chemistry 22 18458088
2022 ATF5 is a regulator of exercise-induced mitochondrial quality control in skeletal muscle. Molecular metabolism 21 36332794
2024 ATF5-Mediated Mitochondrial Unfolded Protein Response (UPRmt) Protects Neurons Against Oxygen-Glucose Deprivation and Cerebral Ischemia. Stroke 19 38913800
2021 ATF5, a putative therapeutic target for the mitochondrial DNA 3243A > G mutation-related disease. Cell death & disease 19 34262025
2019 Dominant-negative ATF5 rapidly depletes survivin in tumor cells. Cell death & disease 19 31551409
2012 ATF5, a possible regulator of osteogenic differentiation in human adipose-derived stem cells. Journal of cellular biochemistry 19 22442021
2024 CTRP3 alleviates mitochondrial dysfunction and oxidative stress injury in pathological cardiac hypertrophy by activating UPRmt via the SIRT1/ATF5 axis. Cell death discovery 18 38278820
2024 METTL14 attenuates cancer stemness by suppressing ATF5/WDR74/β-catenin axis in gastric cancer. Cancer science 18 39497511
2005 ATF5 increases cisplatin-induced apoptosis through up-regulation of cyclin D3 transcription in HeLa cells. Biochemical and biophysical research communications 18 16300731
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
2017 The neuroprotective transcription factor ATF5 is decreased and sequestered into polyglutamine inclusions in Huntington's disease. Acta neuropathologica 17 28861715
2015 Activating transcription factor 5 (ATF5) is essential for the maturation and survival of mouse basal vomeronasal sensory neurons. Cell and tissue research 17 26395637
2021 ATF5 and HIF1α cooperatively activate HIF1 signaling pathway in esophageal cancer. Cell communication and signaling : CCS 16 33980247
2007 Association analysis of ATF4 and ATF5, genes for interacting-proteins of DISC1, in bipolar disorder. Neuroscience letters 16 17346882
2023 ATF5 Attenuates the Secretion of Pro-Inflammatory Cytokines in Activated Microglia. International journal of molecular sciences 15 36834738
2021 Activating transcription factor 5 (ATF5) promotes tumorigenic capability and activates the Wnt/b-catenin pathway in bladder cancer. Cancer cell international 15 34895217
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
2024 Salvianolic acid B improves mitochondrial dysfunction of septic cardiomyopathy via enhancing ATF5-mediated mitochondrial unfolded protein response. Toxicology and applied pharmacology 14 39153513
2023 ATF5-regulated Mitochondrial Unfolded Protein Response Attenuates Neuronal Damage in Epileptic Rat by Reducing Endoplasmic Reticulum Stress Through Mitochondrial ROS. Neurochemical research 14 37847329
2023 ATF5 promotes malignant T cell survival through the PI3K/AKT/mTOR pathway in cutaneous T cell lymphoma. Frontiers in immunology 14 38223508
2022 ATF5 Attenuates Apoptosis in Hippocampal Neurons with Seizures Evoked by Mg2+-Free Medium via Regulating Mitochondrial Unfolded Protein Response. Neurochemical research 14 35939173
2024 Trimethylamine-N-oxide accelerates osteoporosis by PERK activation of ATF5 unfolding. Cellular and molecular life sciences : CMLS 13 39719538
2022 The mitochondrial UPR regulator ATF5 promotes intestinal barrier function via control of the satiety response. Cell reports 13 36516750
2024 The mitochondrial UPR induced by ATF5 attenuates intervertebral disc degeneration via cooperating with mitophagy. Cell biology and toxicology 12 38472656
2024 AMPK Suppression Due to Obesity Drives Oocyte mtDNA Heteroplasmy via ATF5-POLG Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 12 38499990
2023 ATF5 Attenuates Low-magnesium-induced Apoptosis by Inhibiting Endoplasmic Reticulum Stress Via the Regulation of Mitochondrial Reactive Oxygen Species. Neuroscience 12 37913858
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
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
2025 Stiff extracellular matrix activates the transcription factor ATF5 to promote the proliferation of cancer cells. iScience 8 40124511
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
2021 Effect of AAV-mediated overexpression of ATF5 and downstream targets of an integrated stress response in murine skeletal muscle. Scientific reports 8 34611283
2023 mTORC2 orchestrates monocytic and granulocytic lineage commitment by an ATF5-mediated pathway. iScience 7 37649699
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
2024 ATF5-mediated mitochondrial unfolded protein response protects against Pb-induced mitochondria damage in SH-SY5Y cell. Neurotoxicology 5 39547369
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

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