Disease relevance of ATF5

• ATF5 transcription factor plays an essential role in hematopoietic and glioma cell survival and neuronal cell differentiation [1].
• Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5 [2].
• The bZIP transcription factor ATFx binds human T-cell leukemia virus type 1 (HTLV-1) Tax and represses HTLV-1 long terminal repeat-mediated transcription [3].

High impact information on ATF5

• The predicted Fez1 protein contained a leucine-zipper region with similarity to the DNA-binding domain of the cAMP-responsive activating-transcription factor 5 [4].
• Two of these interactants are repressors of cyclic AMP (cAMP)-induced transcription: hICERIIgamma, a product of the CREM gene, and hATF5, a novel ATF homolog [5].
• In a proof-of-principle experiment, retroviral delivery of a function-blocking mutant form of ATF5 into a rat glioma model evokes death of the infected tumor cells, but not of infected brain cells outside the tumors [2].
• The widespread expression of ATF5 in glioblastomas and the selective effect of interference with ATF5 function/expression on their survival suggest that ATF5 may be an attractive target for therapeutic intervention in such tumors [2].
• We found expression of the bZip transcription factor ATF5 in all 29 human glioblastomas and eight human and rat glioma cell lines assessed [2].

Biological context of ATF5

• In contrast, ATF5 does not transactivate cAMP response element (CRE)-containing reporter genes [6].
• Here we show that overexpression of the bZIP protein ATF5, a transcriptional activator, stimulates asparagine synthetase promoter/reporter gene transcription via the nutrient-sensing response unit [6].
• ATF5 increases cisplatin-induced apoptosis through up-regulation of cyclin D3 transcription in HeLa cells [1].
• Interference with ATF5 function or expression in all glioma cell lines tested causes marked apoptotic cell death [2].
• Both transcripts harbor highly complex 5' untranslated regions that impede translation of the ATF5 open reading frame [7].

Anatomical context of ATF5

• In contrast, such manipulations do not affect survival of ATF5-expressing cultured astrocytes or of several other cell types that express this protein [2].
• This suggests a role for ATF5 in odorant sensory neuron differentiation [7].
• In attached clonal neurosphere cultures ATF5 is expressed by neural stem/progenitor cells and is undetectable in tau-positive neurons [8].

Associations of ATF5 with chemical compounds

• Moreover, rapamycin had no effect on basal ATF5 mRNA expression or on increased expression induced by glutamine limitation [9].
• Northern-blot analysis demonstrated that limitation of a single amino acid, glutamine, methionine, or leucine, resulted in increased ATF5 mRNA levels in HeLaS3 cells [9].

Regulatory relationships of ATF5

• The findings imply that the expression of activin betaE, Id2 and ATF5 was tightly regulated by RASSF1A and may associate with its tumor suppressor function [10].

Other interactions of ATF5

• Regulation of asparagine synthetase gene transcription by the basic region leucine zipper transcription factors ATF5 and CHOP [6].
• The ectopic expression of ATF5 in HeLa cells could markedly increase cisplatin-induced apoptosis and the cleavage of Caspase-3, and induce Cyclin D3 mRNA expression via cooperation with E2F1 transcription factor [1].
• The results indicated that apart from the two subunits of cellular RNA polymerase complex, BTF3 and ATF5, this nsp10 protein was also able to interact specifically with the NADH 4L subunit and cytochrome oxidase II [11].

Analytical, diagnostic and therapeutic context of ATF5

• Confocal microscopy analysis showed that Cyclin D3 could colocalize with hATF5 in the nuclear region [12].

References