Genomes and Genes
activating transcription factor 2
Summary: An activating transcription factor that regulates expression of a variety of GENES including C-JUN GENES; CYCLIN A; CYCLIN D1; and ACTIVATING TRANSCRIPTION FACTOR 3.
- Bhoumik A, Fichtman B, DeRossi C, Breitwieser W, Kluger H, Davis S, et al. Suppressor role of activating transcription factor 2 (ATF2) in skin cancer. Proc Natl Acad Sci U S A. 2008;105:1674-9 pubmed publisherb>Activating transcription factor 2 (ATF2) regulates transcription in response to stress and growth factor stimuli. Here, we use a mouse model in which ATF2 was selectively deleted in keratinocytes...
- Lee S, Bahn J, Whitlock N, Baek S. Activating transcription factor 2 (ATF2) controls tolfenamic acid-induced ATF3 expression via MAP kinase pathways. Oncogene. 2010;29:5182-92 pubmed publisher..The current study shows that TA stimulates ATF3 expression and subsequently induces apoptosis. These pathways are mediated through phosphorylation of ATF2, which is mediated by p38 MAPK-, JNK- and ERK-dependent pathways. ..
- Lewis J, Vijayanathan V, Thomas T, Pestell R, Albanese C, Gallo M, et al. Activation of cyclin D1 by estradiol and spermine in MCF-7 breast cancer cells: a mechanism involving the p38 MAP kinase and phosphorylation of ATF-2. Oncol Res. 2005;15:113-28 pubmed..These results indicate that spermine can enhance E2-induced cell signaling and cyclin D1 transcription by activation of the p38 MAP kinase and phosphorylation of ATF-2, contributing to breast cancer cell proliferation. ..
- Tesz G, Guilherme A, Guntur K, Hubbard A, Tang X, Chawla A, et al. Tumor necrosis factor alpha (TNFalpha) stimulates Map4k4 expression through TNFalpha receptor 1 signaling to c-Jun and activating transcription factor 2. J Biol Chem. 2007;282:19302-12 pubmed..p38 stress-activated protein kinase and their downstream transcription factor substrates c-Jun and activating transcription factor 2 (ATF2). siRNA-based depletion of c-Jun and ATF2 attenuated TNFalpha action on Map4k4 mRNA expression...
- Liu Y, Wang Y, Li W, Zheng P, Liu Y. Activating transcription factor 2 and c-Jun-mediated induction of FoxP3 for experimental therapy of mammary tumor in the mouse. Cancer Res. 2009;69:5954-60 pubmed publisher..A low dose of anisomycin was also remarkably effective in treating established mammary tumor in the mice. Our data showed that FoxP3 can be reactivated for cancer therapy. ..
- Torok A, Bouton A, Goldberg J. Helicobacter pylori induces interleukin-8 secretion by Toll-like receptor 2- and Toll-like receptor 5-dependent and -independent pathways. Infect Immun. 2005;73:1523-31 pubmed..pylori induces IL-8 secretion through a dual mechanism that includes a TLR2/5-independent component involving the activities of JNK and ERK and a TLR2/5-dependent component that requires p38 activity. ..
- Bailey J, Europe Finner G. Identification of human myometrial target genes of the c-Jun NH2-terminal kinase (JNK) pathway: the role of activating transcription factor 2 (ATF2) and a novel spliced isoform ATF2-small. J Mol Endocrinol. 2005;34:19-35 pubmedb>Activating transcription factor 2 (ATF2), a ubiquitously expressed member of the basic region leucine zipper (bZIP) family of transcription factors activated by mitogen activated protein kinase (MAPK) pathways, is important in the ..
- Bhoumik A, Gangi L, RONAI Z. Inhibition of melanoma growth and metastasis by ATF2-derived peptides. Cancer Res. 2004;64:8222-30 pubmed..Our study points to mechanisms underlying the activities of the ATF2 peptide while highlighting its possible use in drug design. ..
- Davidson W, Frego L, Peet G, Kroe R, Labadia M, Lukas S, et al. Discovery and characterization of a substrate selective p38alpha inhibitor. Biochemistry. 2004;43:11658-71 pubmed
- Gould Rothberg B, Berger A, Molinaro A, Subtil A, Krauthammer M, Camp R, et al. Melanoma prognostic model using tissue microarrays and genetic algorithms. J Clin Oncol. 2009;27:5772-80 pubmed publisher..72; 95% CI, 1.12 to 6.58; P = .027) cohorts. This multimarker prognostic assay, an independent determinant of melanoma survival, might be beneficial in improving the selection of stage II patients for adjuvant therapy. ..
- Miyata Y, Fukuhara A, Otsuki M, Shimomura I. Expression of activating transcription factor 2 in inflammatory macrophages in obese adipose tissue. Obesity (Silver Spring). 2013;21:731-6 pubmed publisher..b>Activating transcription factor 2 (ATF2) is a member of the ATF/cAMP response element binding family of transcription factors and ..
- Song H, Ki S, Kim S, Moon A. Activating transcription factor 2 mediates matrix metalloproteinase-2 transcriptional activation induced by p38 in breast epithelial cells. Cancer Res. 2006;66:10487-96 pubmed
- Ma Q, Li X, Vale Cruz D, Brown M, Beier F, Luvalle P. Activating transcription factor 2 controls Bcl-2 promoter activity in growth plate chondrocytes. J Cell Biochem. 2007;101:477-87 pubmedb>Activating transcription factor 2 (ATF-2) is expressed ubiquitously in mammals. Mice deficient in ATF-2 (ATF-2 m/m) are slightly smaller than their normal littermates at birth...
- Kim E, Sohn Y, Moon A. TGF-beta-induced transcriptional activation of MMP-2 is mediated by activating transcription factor (ATF)2 in human breast epithelial cells. Cancer Lett. 2007;252:147-56 pubmed..Taken together, this study demonstrates that ATF2 mediates the TGF-beta-induced MMP-2 transcriptional activation, elucidating a molecular mechanism for the malignant progression of human breast epithelial cells exerted by TGF-beta. ..
- Bruhat A, Cherasse Y, Maurin A, Breitwieser W, Parry L, Deval C, et al. ATF2 is required for amino acid-regulated transcription by orchestrating specific histone acetylation. Nucleic Acids Res. 2007;35:1312-21 pubmed..of CHOP (a CCAAT/enhancer-binding protein-related gene) by amino acid deprivation involves the activating transcription factor 2 (ATF2) and the activating transcription factor 4 (ATF4) binding the amino acid response element (..
- Bhoumik A, Lopez Bergami P, RONAI Z. ATF2 on the double - activating transcription factor and DNA damage response protein. Pigment Cell Res. 2007;20:498-506 pubmed..Such changes impact the activity of downstream substrates, including transcription factors. The activating transcription factor 2 (ATF2) has been implicated in malignant and non-malignant skin tumor developments...
- Deng X, Liu H, Huang J, Cheng L, Keller E, Parsons S, et al. Ionizing radiation induces prostate cancer neuroendocrine differentiation through interplay of CREB and ATF2: implications for disease progression. Cancer Res. 2008;68:9663-70 pubmed publisher..element binding transcription factors, cyclic AMP-response element binding protein (CREB) and activating transcription factor 2 (ATF2), function as a transcriptional activator and a repressor, respectively, of NE-like ..
- Hong S, Choi H, Park M, Kim Y, Choi Y, Kim H, et al. Activation and interaction of ATF2 with the coactivator ASC-2 are responsive for granulocytic differentiation by retinoic acid. J Biol Chem. 2004;279:16996-7003 pubmed
- Bhoumik A, RONAI Z. ATF2: a transcription factor that elicits oncogenic or tumor suppressor activities. Cell Cycle. 2008;7:2341-5 pubmed..These findings suggest tissue- and tumor-specific function of ATF2. This review summarizes the current understanding of ATF2 regulation and function. ..
- Lopez Bergami P, Lau E, RONAI Z. Emerging roles of ATF2 and the dynamic AP1 network in cancer. Nat Rev Cancer. 2010;10:65-76 pubmed publisher..This Perspective summarizes our current understanding of the changes in members of the AP1 complex and the role of ATF2 as part of this complex in tumorigenesis. ..
- Li T, Gao L, Sheu T, Sampson E, Flick L, Konttinen Y, et al. Aberrant hypertrophy in Smad3-deficient murine chondrocytes is rescued by restoring transforming growth factor beta-activated kinase 1/activating transcription factor 2 signaling: a potential clinical implication for osteoarthritis. Arthritis Rheum. 2010;62:2359-69 pubmed publisher..significance of Smad3 in the progression of osteoarthritis (OA), the crosstalk between Smad3 and activating transcription factor 2 (ATF-2) in the transforming growth factor beta (TGFbeta) signaling pathway, and the effects of ATF-2 ..
- Xiao L, Rao J, Zou T, Liu L, Yu T, Zhu X, et al. Induced ATF-2 represses CDK4 transcription through dimerization with JunD inhibiting intestinal epithelial cell growth after polyamine depletion. Am J Physiol Cell Physiol. 2010;298:C1226-34 pubmed publisher..These results indicate that induced ATF-2/JunD association following polyamine depletion represses CDK4 transcription, thus contributing to the inhibition of IEC growth. ..
- Ma C, Ying C, Yuan Z, Song B, Li D, Liu Y, et al. dp5/HRK is a c-Jun target gene and required for apoptosis induced by potassium deprivation in cerebellar granule neurons. J Biol Chem. 2007;282:30901-9 pubmed..Taken together, these results suggest that dp5 is a target gene of c-Jun and plays a critical role in potassium deprivation-induced apoptosis in cerebellar granule neurons. ..
- Steinmüller L, Thiel G. Regulation of gene transcription by a constitutively active mutant of activating transcription factor 2 (ATF2). Biol Chem. 2003;384:667-72 pubmedb>Activating transcription factor 2 (ATF2) belongs to the family of basic region leucine zipper (bZIP) proteins that are characterized by the presence of a basic domain that functions as the DNA-binding domain and a leucine zipper domain ..
- Lau E, Ronai Z. ATF2 - at the crossroad of nuclear and cytosolic functions. J Cell Sci. 2012;125:2815-24 pubmed publisher..b>Activating transcription factor 2 (ATF2; also known as cAMP-dependent transcription factor ATF-2) has oncogenic activities in melanoma ..
- Bhoumik A, Takahashi S, Breitweiser W, Shiloh Y, Jones N, RONAI Z. ATM-dependent phosphorylation of ATF2 is required for the DNA damage response. Mol Cell. 2005;18:577-87 pubmedb>Activating transcription factor 2 (ATF2) is regulated by JNK/p38 in response to stress. Here, we demonstrate that the protein kinase ATM phosphorylates ATF2 on serines 490 and 498 following ionizing radiation (IR)...
- Ricote M, García Tuñón I, Bethencourt F, Fraile B, Onsurbe P, Paniagua R, et al. The p38 transduction pathway in prostatic neoplasia. J Pathol. 2006;208:401-7 pubmed
- Agelopoulos M, Thanos D. Epigenetic determination of a cell-specific gene expression program by ATF-2 and the histone variant macroH2A. EMBO J. 2006;25:4843-53 pubmed..siRNA against ATF-2 or macroH2A rescues IL-8 transcription in B cells. Thus, a transcription factor can work as a transcriptional repressor by orchestrating and maintaining the assembly of specialized local chromatin architectures. ..
- Hirose N, Maekawa T, Shinagawa T, Ishii S. ATF-2 regulates lipopolysaccharide-induced transcription in macrophage cells. Biochem Biophys Res Commun. 2009;385:72-7 pubmed publisher..Thus, ATF-2 plays an important role in TLR-mediated transcriptional control in macrophage cells. ..
- Takasawa S, Ikeda T, Akiyama T, Nata K, Nakagawa K, Shervani N, et al. Cyclin D1 activation through ATF-2 in Reg-induced pancreatic beta-cell regeneration. FEBS Lett. 2006;580:585-91 pubmed..These results indicate that the Reg-Reg receptor system stimulates the PI(3)K/ATF-2/cyclin D1 signaling pathway to induce beta-cell regeneration. ..
- Liu H, Deng X, Shyu Y, Li J, Taparowsky E, Hu C. Mutual regulation of c-Jun and ATF2 by transcriptional activation and subcellular localization. EMBO J. 2006;25:1058-69 pubmed..Together, these findings demonstrate that ATF2 and c-Jun mutually regulate each other by altering the dynamics of subcellular localization and by positively impacting transcriptional activity. ..
- Lin D, Chang I, Tseng A, Wu M, Chen C, Patenaude C, et al. Transforming growth factor beta up-regulates cysteine-rich protein 2 in vascular smooth muscle cells via activating transcription factor 2. J Biol Chem. 2008;283:15003-14 pubmed publisher..Our results show for the first time in VSMC that TGFbeta activates ATF2 phosphorylation and Csrp2 gene expression via a CRE promoter element. ..
- Ackermann J, Ashton G, Lyons S, James D, Hornung J, Jones N, et al. Loss of ATF2 function leads to cranial motoneuron degeneration during embryonic mouse development. PLoS ONE. 2011;6:e19090 pubmed publisher..It also confirms that ATF2 has a critical role in limiting the activities of stress kinases JNK and p38 which are potent inducers of cell death in the CNS. ..
- Aggeli I, Gaitanaki C, Beis I. Involvement of JNKs and p38-MAPK/MSK1 pathways in H2O2-induced upregulation of heme oxygenase-1 mRNA in H9c2 cells. Cell Signal. 2006;18:1801-12 pubmed..Our results show for the first time the potential role of JNKs, p38-MAPK and MSK1 in the mechanism of transducing the oxidative stress-signal to HOX-1, possibly promoting cell survival and preserving homeostasis. ..
- Zhang S, Liu H, Liu J, Tse C, Dragunow M, Cooper G. Activation of activating transcription factor 2 by p38 MAP kinase during apoptosis induced by human amylin in cultured pancreatic beta-cells. FEBS J. 2006;273:3779-91 pubmed..We further showed that hA elicits time-dependent activation of activating transcription factor 2 (ATF-2), which was largely suppressed by SB203580, indicating that this activation is catalyzed ..
- Pearson A, Curtis M, Waldvogel H, Faull R, Dragunow M. Activating transcription factor 2 expression in the adult human brain: association with both neurodegeneration and neurogenesis. Neuroscience. 2005;133:437-51 pubmedb>Activating transcription factor 2 (ATF2) is a member of the activator protein-1 family of transcription factors, which includes c-Jun and c-Fos...
- Morton S, Davis R, Cohen P. Signalling pathways involved in multisite phosphorylation of the transcription factor ATF-2. FEBS Lett. 2004;572:177-83 pubmed..In JNK-deficient cells, p38 MAPK substituted for JNK partially in the phosphorylation of Thr69 and p38 MAPK or ERK1/2 in the phosphorylation of Thr71. JNK was the only MAP kinase that phosphorylated Ser90 under the conditions examined. ..
- Kojima M, Suzuki T, Maekawa T, Ishii S, Sumi Ichinose C, Nomura T, et al. Increased expression of tyrosine hydroxylase and anomalous neurites in catecholaminergic neurons of ATF-2 null mice. J Neurosci Res. 2008;86:544-52 pubmed..These data suggest that ATF-2 plays critical roles for proper expression of the TH gene and for neurite extension of catecholaminergic neurons, possibly through a repressor-like action. ..
- Berger A, Kluger H, Li N, Kielhorn E, Halaban R, RONAI Z, et al. Subcellular localization of activating transcription factor 2 in melanoma specimens predicts patient survival. Cancer Res. 2003;63:8103-7 pubmedThe transcription factor activating transcription factor 2 (ATF2) has been shown to be associated with melanocytic oncogenesis and melanoma tumor proliferation in preclinical models...
- Lau E, Kluger H, Varsano T, Lee K, Scheffler I, Rimm D, et al. PKC? promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Cell. 2012;148:543-55 pubmed publisher..In melanoma tumor samples, high PKC? levels associate with poor prognosis. Overall, our findings provide the framework for understanding how subcellular localization enables ATF2 oncogenic or tumor suppressor functions. ..
- Ouwens D, de Ruiter N, van der Zon G, Carter A, Schouten J, van der Burgt C, 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;21:3782-93 pubmed..These results reveal a so far unknown mechanism by which distinct MAPK pathways and Ras effector pathways cooperate to activate a transcription factor. ..
- Salameh A, Galvagni F, Anselmi F, De Clemente C, Orlandini M, Oliviero S. Growth factor stimulation induces cell survival by c-Jun. ATF2-dependent activation of Bcl-XL. J Biol Chem. 2010;285:23096-104 pubmed publisher..AFT2 dimer, which induces the expression of the anti-apoptotic factor Bcl-X(L) that mediates a pro-survival response. ..
- Okamura T, Shimizu H, Nagao T, Ueda R, Ishii S. ATF-2 regulates fat metabolism in Drosophila. Mol Biol Cell. 2007;18:1519-29 pubmed..Furthermore we showed that dATF-2 positively regulated dPEPCK gene transcription via several CRE half-sites in the PEPCK promoter. Thus, dATF-2 is critical for regulation of fat metabolism. ..
- Oka S, Kimura S, Toshida T, Ota R, Yamashita A, Sugiura T. Lysophosphatidylinositol induces rapid phosphorylation of p38 mitogen-activated protein kinase and activating transcription factor 2 in HEK293 cells expressing GPR55 and IM-9 lymphoblastoid cells. J Biochem. 2010;147:671-8 pubmed publisher..The exposure of GPR55-expressing cells to LPI also triggered the phosphorylation of activating transcription factor 2 downstream of the p38 mitogen-activated protein kinase...
- Melnikova V, Bar Eli M. Transcriptional control of the melanoma malignant phenotype. Cancer Biol Ther. 2008;7:997-1003 pubmed..Similar to the case of oncogene addiction, the tumorigenicity and metastatic potential of melanoma can be greatly inhibited by altering the activity of the above-named transcription factors, therefore indicating new treatment prospects. ..
- Zhang J, Jiang H, Gao W, Wu J, Peng K, Shi Y, et al. The JNK/AP1/ATF2 pathway is involved in H2O2-induced acetylcholinesterase expression during apoptosis. Cell Mol Life Sci. 2008;65:1435-45 pubmed publisher..The AP1-like element binds to the transcription factors, c-jun and ATF2, while the ATF2 element binds mainly ATF2. Taken together, our results strongly suggest that H2O2 induces AChE expression via the JNK/AP1/ ATF2 signaling pathway. ..
- Hisatsune J, Yamasaki E, Nakayama M, Shirasaka D, Kurazono H, Katagata Y, et al. Helicobacter pylori VacA enhances prostaglandin E2 production through induction of cyclooxygenase 2 expression via a p38 mitogen-activated protein kinase/activating transcription factor 2 cascade in AZ-521 cells. Infect Immun. 2007;75:4472-81 pubmed..but not a mutated cis-acting replication element (CRE) site, suggesting direct involvement of the activating transcription factor 2 (ATF-2)/CREB-binding region in VacA-induced COX-2 promoter activation...
- Sangerman J, Lee M, Yao X, Oteng E, Hsiao C, Li W, et al. Mechanism for fetal hemoglobin induction by histone deacetylase inhibitors involves gamma-globin activation by CREB1 and ATF-2. Blood. 2006;108:3590-9 pubmed..The data presented herein demonstrate that gamma-gene induction by butyrate and trichostatin A involves ATF-2 and CREB1 activation via p38 MAPK signaling. ..
- Sevilla A, Santos C, Vega F, Lazo P. Human vaccinia-related kinase 1 (VRK1) activates the ATF2 transcriptional activity by novel phosphorylation on Thr-73 and Ser-62 and cooperates with JNK. J Biol Chem. 2004;279:27458-65 pubmed..VRK1 is an element of a novel signaling pathway that regulates gene transcription. ..
- Bhoumik A, Huang T, Ivanov V, Gangi L, Qiao R, Woo S, et al. An ATF2-derived peptide sensitizes melanomas to apoptosis and inhibits their growth and metastasis. J Clin Invest. 2002;110:643-50 pubmed..Growth and metastasis of SW1 and B16F10 mouse melanomas were inhibited by ATF2(50-100) to varying degrees up to a complete regression, depending on the mode (inducible, constitutive, or adenoviral delivery) of its expression. ..
- Towers E, Gilley J, Randall R, Hughes R, Kristiansen M, Ham J. The proapoptotic dp5 gene is a direct target of the MLK-JNK-c-Jun pathway in sympathetic neurons. Nucleic Acids Res. 2009;37:3044-60 pubmed publisher..These results suggest that part of the mechanism by which the MLK-JNK-c-Jun pathway promotes neuronal apoptosis is by activating the transcription of the dp5 gene. ..
- Averous J, Bruhat A, Jousse C, Carraro V, Thiel G, Fafournoux P. Induction of CHOP expression by amino acid limitation requires both ATF4 expression and ATF2 phosphorylation. J Biol Chem. 2004;279:5288-97 pubmed..transcriptional activation of the human CHOP gene by leucine starvation and shown that it binds the activating transcription factor 2 (ATF2)...