HCSGD entry for ATF4

1. General information

Official gene symbolATF4
Entrez ID468
Gene full nameactivating transcription factor 4
Other gene symbolsCREB-2 CREB2 TAXREB67 TXREB
Links to Entrez GeneLinks to Entrez Gene

2. Neighbors in the network

color bar

3. Gene ontology annotation

GO ID

GO term

Evidence

Category

GO:0003677DNA bindingIDA ISSmolecular_function
GO:0003700Sequence-specific DNA binding transcription factor activityISS TASmolecular_function
GO:0005515Protein bindingIPImolecular_function
GO:0005634NucleusIDA ISScellular_component
GO:0005654NucleoplasmTAScellular_component
GO:0005667Transcription factor complexIEAcellular_component
GO:0005737CytoplasmISScellular_component
GO:0005815Microtubule organizing centerIEAcellular_component
GO:0006094GluconeogenesisISSbiological_process
GO:0006355Regulation of transcription, DNA-templatedISSbiological_process
GO:0006366Transcription from RNA polymerase II promoterISSbiological_process
GO:0006520Cellular amino acid metabolic processTASbiological_process
GO:0006987Activation of signaling protein activity involved in unfolded protein responseTASbiological_process
GO:0007214Gamma-aminobutyric acid signaling pathwayIEAbiological_process
GO:0008022Protein C-terminus bindingIEAmolecular_function
GO:0030968Endoplasmic reticulum unfolded protein responseTASbiological_process
GO:0032590Dendrite membraneIEAcellular_component
GO:0034976Response to endoplasmic reticulum stressIDAbiological_process
GO:0043267Negative regulation of potassium ion transportIEAbiological_process
GO:0043525Positive regulation of neuron apoptotic processISSbiological_process
GO:0043565Sequence-specific DNA bindingIEAmolecular_function
GO:0044267Cellular protein metabolic processTASbiological_process
GO:0045893Positive regulation of transcription, DNA-templatedIDA IMP ISS NASbiological_process
GO:0045944Positive regulation of transcription from RNA polymerase II promoterIMP ISSbiological_process
GO:0070059Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stressISSbiological_process
Entries Per Page
Displaying Page of

4. Expression levels in datasets

  • Meta-analysis result

p-value upp-value downFDR upFDR down
0.36354508190.12125356940.99999024730.6693614094

  • Individual experiment result
    ( "-" represent NA in the specific microarray platform )

Data sourceUp or downLog fold change
GSE11954Down-0.4137973404
GSE13712_SHEARUp0.2080923029
GSE13712_STATICUp0.0284724628
GSE19018Up0.4263124160
GSE19899_A1Down-0.2196888923
GSE19899_A2Down-0.8201353872
PubMed_21979375_A1Up0.1640357145
PubMed_21979375_A2Down-1.2232221984
GSE35957Up0.0147443276
GSE36640Up0.0575621415
GSE54402Down-0.1836100328
GSE9593Up0.0994646100
GSE43922Down-0.0770751293
GSE24585Down-0.0620972098
GSE37065Down-0.1866634051
GSE28863_A1Down-0.0867802427
GSE28863_A2Up0.1345293817
GSE28863_A3Up0.1624116403
GSE28863_A4Up0.8210012287
GSE48662Up0.0963743384

5. Regulation relationships with compounds/drugs/microRNAs

  • Compounds

Not regulated by compounds

  • Drugs

Name

Drug

Accession number

  • MicroRNAs

  • mirTarBase

MiRNA_name

mirBase ID

miRTarBase ID

Experiment

Support type

References (Pubmed ID)

hsa-miR-214-3pMIMAT0000271MIRT007201Luciferase reporter assayFunctional MTI23223004
hsa-miR-196b-5pMIMAT0001080MIRT042655CLASHFunctional MTI (Weak)23622248
hsa-miR-342-3pMIMAT0000753MIRT043684CLASHFunctional MTI (Weak)23622248
Entries Per Page
Displaying Page of
  • mirRecord
No target information from mirRecord

6. Text-mining results about the gene

Gene occurances in abstracts of cellular senescence-associated articles: 4 abstracts the gene occurs.


PubMed ID of the article

Sentenece the gene occurs

26961881In Per2 mutant and Cry1/2-null cells, the introduction of oncogenes induced expression of ATF4, a potent repressor of cell senescence-associated proteins p16INK4a and p19ARF
26961881Elevated levels of ATF4 were sufficient to suppress expression of these proteins and drive oncogenic transformation
26961881Conversely, in Bmal1-null and Clock mutant cells, the expression of ATF4 was not induced by oncogene introduction, which allowed constitutive expression of p16INK4a and p19ARF triggering cellular senescence
25567807Impact of ER stress-regulated ATF4/p16 signaling on the premature senescence of renal tubular epithelial cells in diabetic nephropathy
25567807Here, we investigated the role of endoplasmic reticulum (ER) stress-regulated activation of transcription factor 4 (ATF4)/p16 signaling in the premature senescence of renal tubular epithelial cells (RTECs) during DN development
25567807In the renal tissues of Type 2 DN patients, we detected an increased number of senescent cells; elevated deposition of advanced glycation end products (AGEs); upregulated expression of ER stress marker, glucose-regulated protein 78; as well as overexpression of ATF4 and p16
25567807Interestingly, AGE-induced p16 expression and premature senescence were successfully attenuated by ER stress inhibitor and ATF4 gene silencing
25567807Moreover, AGE-induced premature senescence was mimicked by ER stress inducers and ATF4 overexpression, while suppressed by p16 gene silencing
25567807In addition, ER stress inducers can augment ATF4 expression
25567807Therefore, our results demonstrate that the ER stress-regulated ATF4/p16 pathway is involved in the premature senescence of RTECs during DN progression
23229510An important effector of the ISR is activating transcription factor 4 (ATF4), a transcription factor that regulates genes involved in redox homeostasis and amino acid metabolism and transport
23229510Because both inhibition and overactivation of the ISR can induce tumor cell death, modulators of ATF4 expression could prove to be clinically useful
23229510In this study, chemical libraries were screened for modulators of ATF4 expression
23229510We identified one compound, E235 (N-(1-benzyl-piperidin-4-yl)-2-(4-fluoro-phenyl)-benzo[d]imidazo[2,1-b]thiazole-7 -carboxamide), that activated the ISR and dose-dependently increased levels of ATF4 in transformed cells
23229510A dose-dependent decrease in viability was observed in several mouse and human tumor cell lines, and knockdown of ATF4 significantly increased the antiproliferative effects of E235
22102693Stress-regulated transcription factor ATF4 promotes neoplastic transformation by suppressing expression of the INK4a/ARF cell senescence factors
22102693Many cancers overexpress ATF4, a stress-induced transcription factor that promotes cell survival under hypoxic conditions and other stresses of the tumor microenvironment, but the potential contributions of ATF4 to oncogenesis itself have been little explored
22102693Here, we report that ATF4 promotes oncogene-induced neoplastic transformation by suppressing the expression of cellular senescence-associated genes
22102693In wild-type cells these oncogenes induced expression of the murine Atf4 gene along with the cyclin-dependent kinase inhibitor Cdkn2a, which encodes the cell senescence-associated proteins p16INK4 and p19ARF
22102693Elevated levels of ATF4 were sufficient to suppress expression of these proteins and drive oncogenic transformation
22102693Conversely, genetic ablation of ATF4 led to constitutive expression of p16INK4a and p19ARF, triggering cellular senescence
22102693Our findings define a central function for ATF4 in promoting oncogenic transformation by suppressing a central pathway of cellular senescence
Entries Per Page
Displaying Page of