Encyclopedia of Signaling Molecules

Living Edition
| Editors: Sangdun Choi

ATF2

  • Jae Youl Cho
  • Tao Yu
  • Yanyan Yang
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-6438-9_101938-1

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.

Keywords

White Adipose Tissue Keratinocyte Chemoattractant Transactivating Capacity Mouse Brain Microvascular Endothelial Cell cAMP Response Element Promoter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. Blasius AL, Beutler B. Intracellular toll-like receptors. Immunity. 2010;32(3):305–15.CrossRefPubMedGoogle Scholar
  6. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 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.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. Claps G, Cheli Y, et al. A transcriptionally inactive ATF2 variant drives melanomagenesis. Cell Rep. 2016;15(9):1884–92.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 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.PubMedGoogle Scholar
  11. De Graeve F, Bahr A, et al. Role of the ATFa/JNK2 complex in Jun activation. Oncogene. 1999;18(23):3491–500.CrossRefPubMedGoogle Scholar
  12. Dinarello CA. Proinflammatory cytokines. Chest. 2000;118(2):503–8.CrossRefPubMedGoogle Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. Endo M, Su L, et al. Activating transcription factor 2 in mesenchymal tumors. Hum Pathol. 2014;45(2):276–84.CrossRefPubMedGoogle Scholar
  15. 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.Google Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 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.CrossRefPubMedGoogle Scholar
  21. 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.CrossRefPubMedGoogle Scholar
  22. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 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.CrossRefPubMedGoogle Scholar
  25. Livingstone C, Patel G, et al. ATF-2 contains a phosphorylation-dependent transcriptional activation domain. EMBO J. 1995;14(8):1785–97.PubMedPubMedCentralGoogle Scholar
  26. 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.PubMedGoogle Scholar
  27. 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.PubMedPubMedCentralGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.PubMedGoogle Scholar
  30. 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.CrossRefGoogle Scholar
  31. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 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.PubMedGoogle Scholar
  33. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. 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.CrossRefPubMedGoogle Scholar
  36. 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.CrossRefPubMedGoogle Scholar
  37. Sano Y, Tokitou F, et al. CBP alleviates the intramolecular inhibition of ATF-2 function. J Biol Chem. 1998;273(44):29098–105.CrossRefPubMedGoogle Scholar
  38. 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.PubMedPubMedCentralGoogle Scholar
  39. 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.PubMedGoogle Scholar
  40. Vlahopoulos SA, Logotheti S, et al. The role of ATF-2 in oncogenesis. Bioessays. 2008;30(4):314–27.CrossRefPubMedGoogle Scholar
  41. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 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.CrossRefPubMedGoogle Scholar
  43. 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.CrossRefPubMedGoogle Scholar
  44. 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.PubMedGoogle Scholar
  45. Yu T, Li YJ, et al. The regulatory role of activating transcription factor 2 in inflammation. Mediators Inflamm. 2014;2014:950472.PubMedPubMedCentralGoogle Scholar
  46. 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.CrossRefGoogle Scholar
  47. 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.CrossRefPubMedGoogle Scholar
  48. 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.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Department of Genetic EngineeringSungkyunkwan UniversitySuwonSouth Korea
  2. 2.Center for Vascular BiologyInstitute for Translational Medicine, Qingdao UniversityQingdaoChina