ATF4

Gene ontology

Molecular function:

• transcription factor activity
• specific RNA polymerase II transcription factor activity
• transcription activator activity
• sequence-specific DNA binding
• protein dimerization activity

Cellular component:

• nucleus
• cytoplasm

Biological process:

• gluconeogenesis
• transcription
• regulation of transcription, DNA-dependent
• amino acid metabolic process
• response to stress
• positive regulation of transcription from RNA polymerase II promoter

Activating transcription factor 4 (tax-responsive enhancer element B67), also known as ATF4, is a human gene.

This gene encodes a transcription factor that was originally identified as a widely expressed mammalian DNA binding protein that could bind a tax-responsive enhancer element in the LTR of HTLV-1. The encoded protein was also isolated and characterized as the cAMP-response element binding protein 2 (CREB-2). The protein encoded by this gene belongs to a family of DNA-binding proteins that includes the AP-1 family of transcription factors, cAMP-response element binding proteins (CREBs) and CREB-like proteins. These transcription factors share a leucine zipper region that is involved in protein-protein interactions, located C-terminal to a stretch of basic amino acids that functions as a DNA binding domain. Two alternative transcripts encoding the same protein have been described. Two pseudogenes are located on the X chromsome at q28 in a region containing a large inverted duplication.^[1]

Further reading

Rutkowski DT, Kaufman RJ (2003). "All roads lead to ATF4.". Dev. Cell 4 (4): 442–4. PMID 12689582.
Nishizawa M, Nagata S (1992). "cDNA clones encoding leucine-zipper proteins which interact with G-CSF gene promoter element 1-binding protein.". FEBS Lett. 299 (1): 36–8. PMID 1371974.
Karpinski BA, Morle GD, Huggenvik J, et al. (1992). "Molecular cloning of human CREB-2: an ATF/CREB transcription factor that can negatively regulate transcription from the cAMP response element.". Proc. Natl. Acad. Sci. U.S.A. 89 (11): 4820–4. PMID 1534408.
Hai T, Curran T (1991). "Cross-family dimerization of transcription factors Fos/Jun and ATF/CREB alters DNA binding specificity.". Proc. Natl. Acad. Sci. U.S.A. 88 (9): 3720–4. PMID 1827203.
Tsujimoto A, Nyunoya H, Morita T, et al. (1991). "Isolation of cDNAs for DNA-binding proteins which specifically bind to a tax-responsive enhancer element in the long terminal repeat of human T-cell leukemia virus type I.". J. Virol. 65 (3): 1420–6. PMID 1847461.
Hai TW, Liu F, Coukos WJ, Green MR (1990). "Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers.". Genes Dev. 3 (12B): 2083–90. PMID 2516827.
Kokame K, Kato H, Miyata T (1997). "Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes.". J. Biol. Chem. 271 (47): 29659–65. PMID 8939898.
Reddy TR, Tang H, Li X, Wong-Staal F (1997). "Functional interaction of the HTLV-1 transactivator Tax with activating transcription factor-4 (ATF4).". Oncogene 14 (23): 2785–92. doi:10.1038/sj.onc.1201119. PMID 9190894.
Liang G, Hai T (1997). "Characterization of human activating transcription factor 4, a transcriptional activator that interacts with multiple domains of cAMP-responsive element-binding protein (CREB)-binding protein.". J. Biol. Chem. 272 (38): 24088–95. PMID 9295363.
Kawai T, Matsumoto M, Takeda K, et al. (1998). "ZIP kinase, a novel serine/threonine kinase which mediates apoptosis.". Mol. Cell. Biol. 18 (3): 1642–51. PMID 9488481.
Outinen PA, Sood SK, Pfeifer SI, et al. (1999). "Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells.". Blood 94 (3): 959–67. PMID 10419887.
Dunham I, Shimizu N, Roe BA, et al. (1999). "The DNA sequence of human chromosome 22.". Nature 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.
Podust LM, Krezel AM, Kim Y (2001). "Crystal structure of the CCAAT box/enhancer-binding protein beta activating transcription factor-4 basic leucine zipper heterodimer in the absence of DNA.". J. Biol. Chem. 276 (1): 505–13. doi:10.1074/jbc.M005594200. PMID 11018027.
Murphy P, Kolstø A (2001). "Expression of the bZIP transcription factor TCF11 and its potential dimerization partners during development.". Mech. Dev. 97 (1-2): 141–8. PMID 11025215.
White JH, McIllhinney RA, Wise A, et al. (2001). "The GABAB receptor interacts directly with the related transcription factors CREB2 and ATFx.". Proc. Natl. Acad. Sci. U.S.A. 97 (25): 13967–72. doi:10.1073/pnas.240452197. PMID 11087824.
He CH, Gong P, Hu B, et al. (2001). "Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation.". J. Biol. Chem. 276 (24): 20858–65. doi:10.1074/jbc.M101198200. PMID 11274184.
Siu F, Bain PJ, LeBlanc-Chaffin R, et al. (2002). "ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene.". J. Biol. Chem. 277 (27): 24120–7. doi:10.1074/jbc.M201959200. PMID 11960987.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.
Bowers AJ, Scully S, Boylan JF (2003). "SKIP3, a novel Drosophila tribbles ortholog, is overexpressed in human tumors and is regulated by hypoxia.". Oncogene 22 (18): 2823–35. doi:10.1038/sj.onc.1206367. PMID 12743605.

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