Activating transcription factor 4
- PMID: 17466566
- DOI: 10.1016/j.biocel.2007.01.020
Activating transcription factor 4
Abstract
Activating transcription factor 4 (ATF4) belongs to the ATF/CREB (activating transcription factor/cyclic AMP response element binding protein) family of basic region-leucine zipper (bZip) transcription factors, which have the consensus binding site cAMP responsive element (CRE). ATF4 has numerous dimerization partners. ATF4 is induced by stress signals including anoxia/hypoxia, endoplasmic reticulum stress, amino acid deprivation, and oxidative stress. ATF4 expression is regulated transcriptionally, translationally via the PERK pathway of eIF2alpha phosphorylation, and posttranslationally by phosphorylation, which targets ATF4 to proteasomal degradation. ATF4 regulates the expression of genes involved in oxidative stress, amino acid synthesis, differentiation, metastasis and angiogenesis. Transgenic studies have demonstrated ATF4 to be involved in hematopoiesis, lens and skeletal development, fertility, proliferation, differentiation, and long-term memory. ATF4 expression is upregulated in cancer. Since ATF4 is induced by tumour microenvironmental factors, and regulates processes relevant to cancer progression, it might serve as a potential therapeutic target in cancer.
Similar articles
-
Transcriptional regulation of activating transcription factor 4 under oxidative stress in retinal pigment epithelial ARPE-19/HPV-16 cells.Invest Ophthalmol Vis Sci. 2011 Mar 2;52(3):1226-34. doi: 10.1167/iovs.10-5775. Invest Ophthalmol Vis Sci. 2011. PMID: 21087962
-
ATF4, an ER stress and hypoxia-inducible transcription factor and its potential role in hypoxia tolerance and tumorigenesis.Curr Mol Med. 2009 May;9(4):411-6. doi: 10.2174/156652409788167096. Curr Mol Med. 2009. PMID: 19519398 Review.
-
Characterization of an activating transcription factor 4 gene containing a consensus phosphorylation site for PKA in the gonads of Xenopus embryos.Zoolog Sci. 2010 Jan;27(1):19-23. doi: 10.2108/zsj.27.19. Zoolog Sci. 2010. PMID: 20064004
-
Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element.J Biol Chem. 2015 Jun 19;290(25):15878-15891. doi: 10.1074/jbc.M114.635144. Epub 2015 Apr 30. J Biol Chem. 2015. PMID: 25931127 Free PMC article.
-
The molecular biology and nomenclature of the activating transcription factor/cAMP responsive element binding family of transcription factors: activating transcription factor proteins and homeostasis.Gene. 2001 Jul 25;273(1):1-11. doi: 10.1016/s0378-1119(01)00551-0. Gene. 2001. PMID: 11483355 Review.
Cited by
-
Cancer-associated fibroblasts-mediated ATF4 expression promotes malignancy and gemcitabine resistance in pancreatic cancer via the TGF-β1/SMAD2/3 pathway and ABCC1 transactivation.Cell Death Dis. 2021 Mar 29;12(4):334. doi: 10.1038/s41419-021-03574-2. Cell Death Dis. 2021. PMID: 33782384 Free PMC article.
-
Rapid ATF4 Depletion Resets Synaptic Responsiveness after cLTP.eNeuro. 2021 Jun 3;8(3):ENEURO.0239-20.2021. doi: 10.1523/ENEURO.0239-20.2021. Print 2021 May-Jun. eNeuro. 2021. PMID: 33980608 Free PMC article.
-
Targeting apoptotic pathways for cancer therapy.J Clin Invest. 2024 Jul 15;134(14):e179570. doi: 10.1172/JCI179570. J Clin Invest. 2024. PMID: 39007268 Free PMC article. Review.
-
A CRE/AP-1-like motif is essential for induced syncytin-2 expression and fusion in human trophoblast-like model.PLoS One. 2015 Mar 17;10(3):e0121468. doi: 10.1371/journal.pone.0121468. eCollection 2015. PLoS One. 2015. PMID: 25781974 Free PMC article.
-
The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Prog Retin Eye Res. 2024 Jan;98:101231. doi: 10.1016/j.preteyeres.2023.101231. Epub 2023 Dec 12. Prog Retin Eye Res. 2024. PMID: 38092262 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
