GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

ATF-4 bZIP domain (IPR004827) associated with transcription factor activity

GO_REF:0000033

Annotation inferences using phylogenetic trees

Phylogenetic inference from ATF4 orthologs supports DNA binding and transcription activator functions

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

DNA-binding and Transcription keywords mapped to appropriate GO terms

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

Nucleus localization from UniProt subcellular location annotation

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on inter-ontology links

Positive regulation of transcription inferred from transcription activator activity

PMID:23661758

Networks of bZIP protein-protein interactions diversified over a billion years of evolution.

Comprehensive analysis of bZIP dimerization networks across species

"We studied the basic region-leucine zipper (bZIP) transcription factors and quantified bZIP dimerization networks for five metazoan and two single-cell species, measuring interactions in vitro for 2891 protein pairs"
ATF-4 participates in heteromeric bZIP interactions

"Metazoans have a higher proportion of heteromeric bZIP interactions and more network complexity than the single-cell species"

PMID:23692540

The general control nonderepressible-2 kinase mediates stress response and longevity induced by target of rapamycin inactivation in Caenorhabditis elegans.

GCN-2 kinase functions upstream of ATF-4 in stress response
ATF-4 (referred to as ATF-5) mediates longevity from TOR pathway inhibition
Nuclear localization of ATF-4 demonstrated

PMID:23791784

Extensive rewiring and complex evolutionary dynamics in a C. elegans multiparameter transcription factor network.

Comprehensive characterization of C. elegans TF interaction networks

"we comprehensively characterize such network rewiring for C. elegans transcription factors (TFs) within and across four newly delineated molecular networks"
ATF-4 participates in TF-TF interaction networks

"Gene duplication results in two identical paralogs that diverge through mutation, leading to loss or gain of interactions with other biomolecules"

PMID:35181679

ATF-4 and hydrogen sulfide signalling mediate longevity in response to inhibition of translation or mTORC1.

ATF-4 is preferentially translated under reduced protein synthesis conditions

"ATF-4 is preferentially translated under conditions of reduced global protein synthesis"
ATF-4 contains two uORFs mediating translational control

"The C. elegans atf-4 ortholog (previously named atf-5) contains two 5′ UTR uORFs"
ATF-4 overexpression extends lifespan 7-44%

"ATF-4 overexpression increased lifespan by 7-44% across >10 independent trials"
ATF-4 activates cth-2 to increase H2S production

"ATF-4 promotes longevity by activating canonical anti-ageing mechanisms, but also by elevating expression of the transsulfuration enzyme CTH-2 to increase hydrogen sulfide (H2S) production"
ATF-4 upregulates heat shock proteins (sip-1, hsp-70, hsp-16.2, hsp-12.3)

"Each of the ATF-4-upregulated chaperone genes sip-1/CRYAA, hsp-70/HSPA1L, hsp-16.2/HSPB1, and hsp-12.3/HSPB2 was required for lifespan extension from ATF-4 overexpression"
ATF-4 localizes to nucleus in multiple somatic tissues

"Transgenic ATF-4-overexpressing animals (ATF-4OE) exhibited nuclear accumulation of ATF-4 in neuronal, hypodermal, and other somatic tissues under unstressed conditions"
ATF-4-driven longevity requires DAF-16, HSF-1, and SKN-1

"Each of those transcription factors is critical for lifespan extension arising from suppression of translation10,11, and we determined that they are also needed for longevity conferred by ATF-4 overexpression"
ATF-4 increases protein persulfidation through cth-2/H2S pathway

"This H2S boost increases protein persulfidation, a protective modification of redox-reactive cysteines"

file:worm/atf-4/atf-4-deep-research-falcon.md

Deep research findings on atf-4 gene function

ATF-4 is a validated ATF4 ortholog that integrates translational and stress signals via uORF-mediated translational control