Historical Background
Activating transcription factor 2 (ATF2) is a member of the leucine zipper family of DNA-binding proteins located on human chromosome 2q32 and was discovered by Maekawa et al. in 1989 (Maekawa et al. 1989). The ATF2 protein consists of 505 amino acids, with phosphorylation sites near the C-terminus at serine residues 472 and 480 in the mouse protein and serine residues 490 and 498 in the human protein. In response to double-stranded DNA breaks, the ataxia telangiectasia-mutant (Yosaatmadja et al. 2015) protein kinase activates ATF2 (Bhoumik et al. 2005). The ATF family of proteins includes seven subtypes based on sequence similarity: ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, and ATF7 (Hummler et al. 1994). A schematic of the ATF2 protein is shown in Fig. 1.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Arora H, Qureshi R, et al. Coordinated regulation of ATF2 by miR-26b in gamma-irradiated lung cancer cells. PLoS One. 2011;6(8):e23802.
Bhoumik A, Takahashi S, et al. ATM-dependent phosphorylation of ATF2 is required for the DNA damage response. Mol Cell. 2005;18(5):577–87.
Bhoumik A, Fichtman B, et al. Suppressor role of activating transcription factor 2 (ATF2) in skin cancer. Proc Natl Acad Sci USA. 2008;105(5):1674–9.
Bickford JS, Newsom KJ, et al. Induction of group IVC phospholipase A2 in allergic asthma: transcriptional regulation by TNFalpha in bronchoepithelial cells. Biochem J. 2012;442(1):127–37.
Blasius AL, Beutler B. Intracellular toll-like receptors. Immunity. 2010;32(3):305–15.
Breitwieser W, Lyons S, et al. Feedback regulation of p38 activity via ATF2 is essential for survival of embryonic liver cells. Genes Dev. 2007;21(16):2069–82.
Brinkman BM, Telliez JB, et al. Engagement of tumor necrosis factor (TNF) receptor 1 leads to ATF-2- and p38 mitogen-activated protein kinase-dependent TNF-alpha gene expression. J Biol Chem. 1999;274(43):30882–6.
Choi CY, Choi BH, et al. Activating transcription factor 2 (ATF2) down-regulates hepatitis B virus X promoter activity by the competition for the activating protein 1 binding site and the formation of the ATF2-Jun heterodimer. J Biol Chem. 1997;272(27):16934–9.
Claps G, Cheli Y, et al. A transcriptionally inactive ATF2 variant drives melanomagenesis. Cell Rep. 2016;15(9):1884–92.
De Cesare D, Vallone D, et al. Heterodimerization of c-Jun with ATF-2 and c-Fos is required for positive and negative regulation of the human urokinase enhancer. Oncogene. 1995;11(2):365–76.
De Graeve F, Bahr A, et al. Role of the ATFa/JNK2 complex in Jun activation. Oncogene. 1999;18(23):3491–500.
Dinarello CA. Proinflammatory cytokines. Chest. 2000;118(2):503–8.
Duffey D, Dolgilevich S, et al. Activating transcription factor-2 in survival mechanisms in head and neck carcinoma cells. Head Neck. 2011;33(11):1586–99.
Endo M, Su L, et al. Activating transcription factor 2 in mesenchymal tumors. Hum Pathol. 2014;45(2):276–84.
Fang JQ, Du JY, et al. Intervention of electroacupuncture on spinal p38 MAPK/ATF-2/VR-1 pathway in treating inflammatory pain induced by CFA in rats. Mol Pain. 2013;9:13.
Gozdecka M, Lyons S, et al. JNK suppresses tumor formation via a gene-expression program mediated by ATF2. Cell Rep. 2014;9(4):1361–74.
Huang Q, Du X, et al. JNK-mediated activation of ATF2 contributes to dopaminergic neurodegeneration in the MPTP mouse model of Parkinson’s disease. Exp Neurol. 2016;277:296–304.
Hummler E, Cole TJ, et al. Targeted mutation of the CREB gene: compensation within the CREB/ATF family of transcription factors. Proc Natl Acad Sci USA. 1994;91(12):5647–51.
Ibrahim SA, Yip GW, et al. Targeting of syndecan-1 by microRNA miR-10b promotes breast cancer cell motility and invasiveness via a Rho-GTPase- and E-cadherin-dependent mechanism. Int J Cancer. 2012;131(6):E884–96.
Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373–84.
Kumar A, Bhatia HS, et al. microRNA-26a modulates inflammatory response induced by toll-like receptor 4 stimulation in microglia. J Neurochem. 2015;135(6):1189–202.
Liao H, Hyman MC, et al. cAMP/CREB-mediated transcriptional regulation of ectonucleoside triphosphate diphosphohydrolase 1 (CD39) expression. J Biol Chem. 2010;285(19):14791–805.
Licht AH, Pein OT, et al. JunB is required for endothelial cell morphogenesis by regulating core-binding factor beta. J Cell Biol. 2006;175(6):981–91.
Lin CC, Hsieh HL, et al. Upregulation of COX-2/PGE2 by ET-1 mediated through Ca2+-dependent signals in mouse brain microvascular endothelial cells. Mol Neurobiol. 2014;49(3):1256–69.
Livingstone C, Patel G, et al. ATF-2 contains a phosphorylation-dependent transcriptional activation domain. EMBO J. 1995;14(8):1785–97.
Lv G, Hu Z, et al. MicroRNA-451 regulates activating transcription factor 2 expression and inhibits liver cancer cell migration. Oncol Rep. 2014;32(3):1021–8.
Maekawa T, Sakura H, et al. Leucine zipper structure of the protein CRE-BP1 binding to the cyclic AMP response element in brain. EMBO J. 1989;8(7):2023–8.
Maekawa T, Jin W, et al. The role of ATF-2 family transcription factors in adipocyte differentiation: antiobesity effects of p38 inhibitors. Mol Cell Biol. 2010;30(3):613–25.
Matsuda S, Maekawa T, et al. Identification of the functional domains of the transcriptional regulator CRE-BP1. J Biol Chem. 1991;266(27):18188–93.
Miyata Y, Fukuhara A, et al. Expression of activating transcription factor 2 in inflammatory macrophages in obese adipose tissue. Obesity (Silver Spring). 2013;21(4):731–6.
Nair S, Barve A, et al. Regulation of Nrf2- and AP-1-mediated gene expression by epigallocatechin-3-gallate and sulforaphane in prostate of Nrf2-knockout or C57BL/6J mice and PC-3 AP-1 human prostate cancer cells. Acta Pharmacol Sin. 2010;31(9):1223–40.
Nomura N, Zu YL, et al. Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1. J Biol Chem. 1993;268(6):4259–66.
Ouwens DM, de Ruiter ND, et al. Growth factors can activate ATF2 via a two-step mechanism: phosphorylation of Thr71 through the Ras-MEK-ERK pathway and of Thr69 through RalGDS-Src-p38. EMBO J. 2002;21(14):3782–93.
Pearson AG, Curtis MA, et al. Activating transcription factor 2 expression in the adult human brain: association with both neurodegeneration and neurogenesis. Neuroscience. 2005;133(2):437–51.
Reimold AM, Kim J, et al. Decreased immediate inflammatory gene induction in activating transcription factor-2 mutant mice. Int Immunol. 2001;13(2):241–8.
Rudraraju B, Droog M, et al. Phosphorylation of activating transcription factor-2 (ATF-2) within the activation domain is a key determinant of sensitivity to tamoxifen in breast cancer. Breast Cancer Res Treat. 2014;147(2):295–309.
Sano Y, Tokitou F, et al. CBP alleviates the intramolecular inhibition of ATF-2 function. J Biol Chem. 1998;273(44):29098–105.
Shen T, Yang WS, et al. AP-1/IRF-3 targeted anti-inflammatory activity of andrographolide isolated from Andrographis paniculata. Evid Based Complement Alternat Med. 2013;2013:210736.
Takeda J, Maekawa T, et al. Expression of the CRE-BP1 transcriptional regulator binding to the cyclic AMP response element in central nervous system, regenerating liver, and human tumors. Oncogene. 1991;6(6):1009–14.
Vlahopoulos SA, Logotheti S, et al. The role of ATF-2 in oncogenesis. Bioessays. 2008;30(4):314–27.
Wu DS, Chen C, et al. ATF2 predicts poor prognosis and promotes malignant phenotypes in renal cell carcinoma. J Exp Clin Cancer Res. 2016;35(1):108.
Xu Y, Liu Z, et al. The effect of JDP2 and ATF2 on the epithelial-mesenchymal transition of human pancreatic cancer cell lines. Pathol Oncol Res. 2012;18(3):571–7.
Yosaatmadja Y, Patterson AV, et al. The 1.65 A resolution structure of the complex of AZD4547 with the kinase domain of FGFR1 displays exquisite molecular recognition. Acta Crystallogr D Biol Crystallogr. 2015;71(Pt 3):525–33.
You Z, Zhou Y, et al. Activating transcription factor 2 expression mediates cell proliferation and is associated with poor prognosis in human non-small cell lung carcinoma. Oncol Lett. 2016;11(1):760–6.
Yu T, Li YJ, et al. The regulatory role of activating transcription factor 2 in inflammation. Mediators Inflamm. 2014;2014:950472.
Zhang R, Luo H, et al. MiR-622 suppresses proliferation, invasion and migration by directly targeting activating transcription factor 2 in glioma cells. J Neuro-Oncol. 2015;121(1):63–72.
Zhang S, Gao L, et al. miRNA-204 suppresses human non-small cell lung cancer by targeting ATF2. Tumour Biol. 2016;37(8):11177–86.
Zhao Y, Li Y, et al. Helicobacter pylori enhances CIP2A expression and cell proliferation via JNK2/ATF2 signaling in human gastric cancer cells. Int J Mol Med. 2014;33(3):703–10.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Cho, J.Y., Yu, T., Yang, Y. (2018). ATF2. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101938
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_101938
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences