transcription factor ap 2


Summary: A family of DNA binding proteins that regulate expression of a variety of GENES during CELL DIFFERENTIATION and APOPTOSIS. Family members contain a highly conserved carboxy-terminal basic HELIX-TURN-HELIX MOTIF involved in dimerization and sequence-specific DNA binding.

Top Publications

  1. Bassett E, Williams T, Zacharias A, Gage P, Fuhrmann S, West Mays J. AP-2alpha knockout mice exhibit optic cup patterning defects and failure of optic stalk morphogenesis. Hum Mol Genet. 2010;19:1791-804 pubmed publisher
    ..In view of recent data showing that mutations in human TFAP2A result in similar eye defects, the current findings demonstrate that AP-2alpha KO mice provide a valuable model for human ocular disease...
  2. Nordquist N, Gokturk C, Comasco E, Nilsson K, Oreland L, Hallman J. Transcription factor AP2 beta involved in severe female alcoholism. Brain Res. 2009;1305 Suppl:S20-6 pubmed publisher
    ..It was observed that the genetic association was restricted to the subset of cases that had not experienced these negative psychosocial factors. ..
  3. Stoetzel C, Riehm S, Bennouna Greene V, Pelletier V, Vigneron J, Leheup B, et al. Confirmation of TFAP2A gene involvement in branchio-oculo-facial syndrome (BOFS) and report of temporal bone anomalies. Am J Med Genet A. 2009;149A:2141-6 pubmed publisher
    ..Moreover, we present CT scan temporal bone anomalies in the familial cases, related to branchial arch defects, highlighting the importance of radiological investigations for differential diagnosis...
  4. Jonckheere N, Fauquette V, Stechly L, Saint Laurent N, Aubert S, Susini C, et al. Tumour growth and resistance to gemcitabine of pancreatic cancer cells are decreased by AP-2alpha overexpression. Br J Cancer. 2009;101:637-44 pubmed publisher
    ..Our data suggested that AP-2alpha overexpression could be exploited to decrease in vivo tumour growth of pancreatic cancer cells and to increase their sensitivity to gemcitabine. ..
  5. Orso F, Jäger R, Calogero R, Schorle H, Sismondi P, De Bortoli M, et al. AP-2alpha regulates migration of GN-11 neurons via a specific genetic programme involving the Axl receptor tyrosine kinase. BMC Biol. 2009;7:25 pubmed publisher
    ..We show that AP-2alpha plays an essential role in cell movement via the activation of cell-specific genetic programmes. Moreover, we demonstrate that the AP-2alpha regulated gene Axl is an essential player in GN-11 neuron migration. ..
  6. Tekin M, Sirmaci A, Yüksel Konuk B, Fitoz S, Sennaroglu L. A complex TFAP2A allele is associated with branchio-oculo-facial syndrome and inner ear malformation in a deaf child. Am J Med Genet A. 2009;149A:427-30 pubmed publisher
    ..Our report implies that the localization of mutations in TFAP2A might be responsible with the phenotypic findings in BOF syndrome. ..
  7. Provenzano M, Yu L, Hitchler M, Fitzgerald M, Robinson R, Wayne S, et al. AP-2 participates in the transcriptional control of the amyloid precursor protein (APP) gene in oral squamous cell carcinoma. Exp Mol Pathol. 2007;83:277-82 pubmed
    ..Taken together, these findings demonstrate a role for the transcription factor AP-2alpha in the regulation of APP gene expression in human keratinocytes. ..
  8. Nilsson K, Sjoberg R, Leppert J, Oreland L, Damberg M. Transcription factor AP-2 beta genotype and psychosocial adversity in relation to adolescent depressive symptomatology. J Neural Transm (Vienna). 2009;116:363-70 pubmed publisher
    ..Amongst carriers of one or two copies of the long allele, there was no difference in depressive symptoms despite differences in psychosocial environments. ..
  9. Kondo M, Maegawa H, Obata T, Ugi S, Ikeda K, Morino K, et al. Transcription factor activating protein-2beta: a positive regulator of monocyte chemoattractant protein-1 gene expression. Endocrinology. 2009;150:1654-61 pubmed publisher
    ..Thus, we propose that AP-2beta positively regulates MCP-1 expression; subsequently contributes to the infiltration of macrophages to adipose tissue; and leads to insulin resistance, type 2 diabetes, and cardiovascular diseases. ..

More Information


  1. Wenke A, Grassel S, Moser M, Bosserhoff A. The cartilage-specific transcription factor Sox9 regulates AP-2epsilon expression in chondrocytes. FEBS J. 2009;276:2494-504 pubmed publisher
    ..This is the first study to prove the direct regulation of AP-2epsilon by the transcription factor Sox9, and to indicate that AP-2epsilon potentially has an important role as a modulator of hypertrophic cartilage. ..
  2. Collaco A, Jakab R, Hegan P, Mooseker M, Ameen N. Alpha-AP-2 directs myosin VI-dependent endocytosis of cystic fibrosis transmembrane conductance regulator chloride channels in the intestine. J Biol Chem. 2010;285:17177-87 pubmed publisher
    ..The findings support alpha-AP-2 in directing myosin VI-dependent endocytosis of CFTR and a requirement for myosin VI in membrane invagination and coated pit formation in enterocytes. ..
  3. Reiber J, Sznajer Y, Posteguillo E, Müller D, Lyonnet S, Baumann C, et al. Additional clinical and molecular analyses of TFAP2A in patients with the branchio-oculo-facial syndrome. Am J Med Genet A. 2010;152A:994-9 pubmed publisher
    ..Our study represents the second group of BOFS patients with molecular confirmation, expanding the phenotype and spectrum of mutations and limiting it to a restricted part of the gene. ..
  4. Al Dosari M, Almazyad M, Al Ebdi L, Mohamed J, Al Dahmash S, Al Dhibi H, et al. Ocular manifestations of branchio-oculo-facial syndrome: report of a novel mutation and review of the literature. Mol Vis. 2010;16:813-8 pubmed
    ..This report expands the ocular phenotypic spectrum of BOFS and adds to the small number of reported TFAP2A mutations. ..
  5. Gallicchio M, Bach L. Advanced glycation end products inhibit Na+ K+ ATPase in proximal tubule epithelial cells: role of cytosolic phospholipase A2alpha and phosphatidylinositol 4-phosphate 5-kinase gamma. Biochim Biophys Acta. 2010;1803:919-30 pubmed publisher
    ..Elucidation of new intracellular AGE signaling pathways may lead to improved therapies for diabetic nephropathy...
  6. Huang T, Liu Y, Huang M, Zhao X, Cheng L. Wnt1-cre-mediated conditional loss of Dicer results in malformation of the midbrain and cerebellum and failure of neural crest and dopaminergic differentiation in mice. J Mol Cell Biol. 2010;2:152-63 pubmed publisher
    ..We then demonstrated that the development of dopaminergic neurons was impaired in Dicer-deleted mice. Our studies therefore suggest that miRNAs contribute to the embryonic development in multiple locations. ..
  7. Tan C, Walsh M, Gelb B. Fgfr3 is a transcriptional target of Ap2delta and Ash2l-containing histone methyltransferase complexes. PLoS ONE. 2009;4:e8535 pubmed publisher
    ..Thus, we have identified several candidate targets of complexes containing Ap2delta and Ash2l that can be used to further elucidate their roles during development and showed that Fgfr3 is a novel direct target of these complexes. ..
  8. El Ouakfaoui S, Schnell J, Abdeen A, Colville A, Labb H, Han S, et al. Control of somatic embryogenesis and embryo development by AP2 transcription factors. Plant Mol Biol. 2010;74:313-26 pubmed publisher
    ..The results provide new insights into the mechanisms by which BBM governs embryogenesis...
  9. Yuda M, Iwanaga S, Shigenobu S, Kato T, Kaneko I. Transcription factor AP2-Sp and its target genes in malarial sporozoites. Mol Microbiol. 2010;75:854-63 pubmed publisher
    ..These results indicate that AP2-Sp is a major transcription factor that regulates gene expression in the sporozoite stage...
  10. Xu B, Qu X, Gu S, Doughman Y, Watanabe M, Dunwoodie S, et al. Cited2 is required for fetal lung maturation. Dev Biol. 2008;317:95-105 pubmed publisher
    ..We propose that the Cited2-Tcfap2c complex controls lung maturation by regulating Cebpa expression. Understanding the function of this complex may provide novel therapeutic strategies for patients with respiratory distress syndromes. ..
  11. Hirono S, Yamaue H, Hoshikawa Y, Ina S, Tani M, Kawai M, et al. Molecular markers associated with lymph node metastasis in pancreatic ductal adenocarcinoma by genome-wide expression profiling. Cancer Sci. 2010;101:259-66 pubmed publisher
    ..These two markers were also associated with survival in patients with resected PDAC. We demonstrate that AP2alpha and MUC17 may serve as potential prognostic molecular markers for LNM in patients with PDAC. ..
  12. Oreland S, Daoura L, Gustafsson Ericson L, Damberg M, Hyytia P, Oreland L, et al. Does the transcription factor AP-2beta have an impact on the genetic and early environmental influence on ethanol consumption?. J Neural Transm (Vienna). 2010;117:1077-81 pubmed publisher
    ..Taken together, we found differences in brainstem TFAP-2beta protein between the AA and ANA rats. ..
  13. Skoblenick K, Argintaru N, Xu Y, Dyck B, Basu D, Tan M, et al. Role of AP-2alpha transcription factor in the regulation of synapsin II gene expression by dopamine D1 and D2 receptors. J Mol Neurosci. 2010;41:267-77 pubmed publisher
  14. Chang T, Yu S, Lin S, Hsiao Y, Chang G, Yang P, et al. Tumor suppressor HLJ1 binds and functionally alters nucleophosmin via activating enhancer binding protein 2alpha complex formation. Cancer Res. 2010;70:1656-67 pubmed publisher
    ..Our findings suggest that HLJ1 switches the role of NPM1, which can act as tumor suppressor or oncogene, by modulating the oligomerization of NPM1 via HLJ1-NPM1 heterodimer formation and recruiting AP-2alpha to the MMP-2 promoter. ..
  15. Meng X, Kondo M, Morino K, Fuke T, Obata T, Yoshizaki T, et al. Transcription factor AP-2beta: a negative regulator of IRS-1 gene expression. Biochem Biophys Res Commun. 2010;392:526-32 pubmed publisher
    ..Based on these findings, we speculate that the AP-2beta transcriptional factor is a unique regulator of IRS-1 and a candidate gene for insulin resistance. ..
  16. Orso F, Cora D, Ubezio B, Provero P, Caselle M, Taverna D. Identification of functional TFAP2A and SP1 binding sites in new TFAP2A-modulated genes. BMC Genomics. 2010;11:355 pubmed publisher
    ..In addition, we demonstrated a fine-tuned regulation of DCBLD2/ESDN transcription by TFAP2A. ..
  17. Wenke A, Bosserhoff A. Roles of AP-2 transcription factors in the regulation of cartilage and skeletal development. FEBS J. 2010;277:894-902 pubmed publisher
    ..This review gives an overview of AP-2s, and discusses the recent findings on the AP-2 family, in particular AP-2alpha, AP-2beta, and AP-2epsilon, as regulators of cartilage and skeletal development. ..
  18. Pauciullo A, Cosenza G, Nicodemo D, Gallo D, Mancusi A, Crepaldi P, et al. Molecular cloning, promoter analysis and SNP identification of Italian Nicastrese and Saanen lactoferrin gene. Vet Immunol Immunopathol. 2010;134:279-83 pubmed publisher
  19. Yu L, Venkataraman S, Coleman M, Spitz D, Wertz P, Domann F. Glutathione peroxidase-1 inhibits UVA-induced AP-2alpha expression in human keratinocytes. Biochem Biophys Res Commun. 2006;351:1066-71 pubmed
    ..Taken together, these findings suggest that GPx-1 inhibits UVA-induced AP-2alpha expression by suppressing the accumulation of H(2)O(2). ..
  20. Williams C, Scibetta A, Friedrich J, Canosa M, Berlato C, Moss C, et al. AP-2gamma promotes proliferation in breast tumour cells by direct repression of the CDKN1A gene. EMBO J. 2009;28:3591-601 pubmed publisher
  21. Pinto L, Drechsel D, Schmid M, Ninkovic J, Irmler M, Brill M, et al. AP2gamma regulates basal progenitor fate in a region- and layer-specific manner in the developing cortex. Nat Neurosci. 2009;12:1229-37 pubmed publisher
    ..Thus, AP2gamma acts as a regulator of basal progenitor fate, linking regional and laminar specification in the mouse developing cerebral cortex. ..
  22. Ailan H, Xiangwen X, Daolong R, Lu G, Xiaofeng D, Xi Q, et al. Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells. BMC Cancer. 2009;9:279 pubmed publisher
    ..This suggested that AP-2gamma can coordinate the expression of a network of genes, involving in carcinogenesis, especially in breast cancer. They could serve as therapeutic targets against breast cancers in the future. ..
  23. Tai T, Wong Faull D, Claycomb R, Aborn J, Wong D. PACAP-regulated phenylethanolamine N-methyltransferase gene expression. J Neurochem. 2010;115:1195-205 pubmed publisher
  24. Thewes V, Orso F, Jäger R, Eckert D, Schäfer S, Kirfel G, et al. Interference with activator protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation-sensitivity in breast cancer cells. BMC Cancer. 2010;10:192 pubmed publisher
    ..Therefore, interference with AP-2 function could increase the sensitivity of tumor cells towards therapeutic intervention. ..
  25. Jäger R, Schäfer S, Hau Liersch M, Schorle H. Loss of transcription factor AP-2gamma/TFAP2C impairs branching morphogenesis of the murine mammary gland. Dev Dyn. 2010;239:1027-33 pubmed publisher
    ..Therefore, AP-2gamma is functionally involved in branching morphogenesis of the mammary epithelium, possibly by controlling genetic processes downstream of ovarian hormones. ..
  26. Laurson J, Khan S, Chung R, Cross K, Raj K. Epigenetic repression of E-cadherin by human papillomavirus 16 E7 protein. Carcinogenesis. 2010;31:918-26 pubmed publisher
  27. Moon U, Kim C, Choi J, Kim Y, Choi Y, Yoon H, et al. AP2alpha is essential for MUC8 gene expression in human airway epithelial cells. J Cell Biochem. 2010;110:1386-98 pubmed publisher
    ..From these results, we concluded that PMA induces MUC8 gene expression through a mechanism involving PKC, ERK1/2, and AP2 alpha activation in human airway epithelial cells. ..
  28. Li X, Glubrecht D, Godbout R. AP2 transcription factor induces apoptosis in retinoblastoma cells. Genes Chromosomes Cancer. 2010;49:819-30 pubmed publisher
    ..We propose that inability to differentiate along the amacrine/horizontal cell lineages may underlie retinoblastoma tumor formation. ..
  29. Wei C, Lin C, Yu Y, Lin C, Lin P, Wu M, et al. n-Butylidenephthalide induced apoptosis in the A549 human lung adenocarcinoma cell line by coupled down-regulation of AP-2alpha and telomerase activity. Acta Pharmacol Sin. 2009;30:1297-306 pubmed publisher
    ..To investigate the role of hTERT gene expression and AP-2alpha in n-butylidenephthalide (n-BP)-induced apoptosis in A549 lung cancer cells...
  30. Yuda M, Iwanaga S, Shigenobu S, Mair G, Janse C, Waters A, et al. Identification of a transcription factor in the mosquito-invasive stage of malaria parasites. Mol Microbiol. 2009;71:1402-14 pubmed publisher
    ..These results indicate that AP2 family TFs have important roles in stage-specific gene regulation in Plasmodium parasites. ..
  31. Jin X, Zhu B, Peng R, Jiang H, Chen J, Zhuang J, et al. Optimizing the binding activity of the AP2/ERF transcription factor with the GCC box element from Brassica napus by directed evolution. BMB Rep. 2010;43:567-72 pubmed
    ..Changes of Gly156 to arginine and Phe62 to serine increased the GCCbinding activity of BnaERF-B3-hy15 and the alter of Gly156 to arginine changed the AP2-domain structure of BnaERF-B3- hy15. ..
  32. Staun Ram E, Goldman S, Shalev E. p53 Mediates epidermal growth factor (EGF) induction of MMP-2 transcription and trophoblast invasion. Placenta. 2009;30:1029-36 pubmed publisher
    ..p53 mediates both basic and EGF-induced MMP-2 transcription. ..
  33. Chen H, Han W, Deng M, Qin J, Yuan D, Liu J, et al. Transcriptional regulation of PP2A-A alpha is mediated by multiple factors including AP-2alpha, CREB, ETS-1, and SP-1. PLoS ONE. 2009;4:e7019 pubmed publisher
    ..ChIP assays further confirm that all the above transcription factors participate the regulation of PP2A-A alpha gene promoter. Together, our results reveal that multiple transcription factors regulate the PP2A-A alpha gene. ..
  34. Yu K, Di G, Fan L, Wu J, Hu Z, Shen Z, et al. A functional polymorphism in the promoter region of GSTM1 implies a complex role for GSTM1 in breast cancer. FASEB J. 2009;23:2274-87 pubmed publisher
    ..We recommend that a more complicated role for GSTM1 should be considered in breast cancer risk prediction. ..
  35. Lee H, Rao J, Chang L, Rapoport S, Kim H. Chronic imipramine but not bupropion increases arachidonic acid signaling in rat brain: is this related to 'switching' in bipolar disorder?. Mol Psychiatry. 2010;15:602-14 pubmed publisher
    ..Mania in bipolar disorder thus may involve upregulated brain AA metabolism. ..
  36. Domenzain Reyna C, Hernandez D, Miquel Serra L, Docampo M, Badenas C, Fabra A, et al. Structure and regulation of the versican promoter: the versican promoter is regulated by AP-1 and TCF transcription factors in invasive human melanoma cells. J Biol Chem. 2009;284:12306-17 pubmed publisher
    ..These results showing that AP-1 and TCF-4 binding sites are the main regulatory regions directing versican production provide new insights into versican promoter regulation during melanoma progression. ..
  37. Arduini B, Bosse K, Henion P. Genetic ablation of neural crest cell diversification. Development. 2009;136:1987-94 pubmed publisher
    ..Our results identify a genetic regulatory pathway functionally discrete from the process of neural crest induction that is required for the initiation of neural crest cell diversification during embryonic development. ..
  38. Wang X, Zhao J, Tang S, Lee S, Glazer R, Hewlett I. c-FLIPL regulates PKC via AP-2 to inhibit Bax-mediated apoptosis induced by HIV-1 gp120 in Jurkat cells. Mol Cell Biochem. 2009;330:23-9 pubmed publisher
    ..Collectively, these findings further corroborate the concept that gp120 plays an important role, via involvement of molecules such as c-FLIPL, in apoptotic cell death due to HIV-1 infection. ..
  39. Li Q, LOHR C, Dashwood R. Activator protein 2alpha suppresses intestinal tumorigenesis in the Apc(min) mouse. Cancer Lett. 2009;283:36-42 pubmed publisher
  40. Pan Y, Viklund I, Tsai H, Pettersson S, Maruyama I. The ulcerative colitis marker protein WAFL interacts with accessory proteins in endocytosis. Int J Biol Sci. 2010;6:163-71 pubmed
    ..Therefore, these results suggest that WAFL may play an important role in endocytosis and subsequent membrane trafficking by interacting with AP2 through KIAA0196 and KIAA1033. ..
  41. Alexandrescu D, Kauffman C, Dasanu C. The cutaneous epidermal growth factor network: Can it be translated clinically to stimulate hair growth?. Dermatol Online J. 2009;15:1 pubmed
    ..A better characterization of the individual roles pertaining to the EGF family ligands and receptors, has the potential provide new strategies for the management of hair loss. ..
  42. Robinson M, Sahlender D, Foster S. Rapid inactivation of proteins by rapamycin-induced rerouting to mitochondria. Dev Cell. 2010;18:324-31 pubmed publisher
    ..This type of approach, which we call a "knocksideways," should be widely applicable as a means of inactivating proteins with a time scale of seconds or minutes rather than days. ..
  43. Kotani T, Iwase A, Ino K, Sumigama S, Yamamoto E, Hayakawa H, et al. Activator protein-2 impairs the invasion of a human extravillous trophoblast cell line. Endocrinology. 2009;150:4376-85 pubmed publisher
    ..The present data suggest that AP-2 may suppress trophoblast migration and invasion, thus leading to a shallow placentation in preeclampsia. ..
  44. Payne S, Serth J, Schostak M, Kamradt J, Strauss A, Thelen P, et al. DNA methylation biomarkers of prostate cancer: confirmation of candidates and evidence urine is the most sensitive body fluid for non-invasive detection. Prostate. 2009;69:1257-69 pubmed publisher
    ..The biomarkers' PCa sensitivity was greater for urine than plasma DNA. The biomarker performances in urine DNA should next be validated in formal training and test studies. ..
  45. Hoare S, Hoare K, Reinhard M, Flagg T, May W. Functional characterization of the murine Tnk1 promoter. Gene. 2009;444:1-9 pubmed publisher
    ..These findings provide a mechanism by which the m-Tnk1 promoter can be dynamically regulated during normal growth. ..
  46. Ugi S, Nishio Y, Yamamoto H, Ikeda K, Kobayashi M, Tsukada S, et al. Relation of the expression of transcriptional factor TFAP2B to that of adipokines in subcutaneous and omental adipose tissues. Obesity (Silver Spring). 2010;18:1277-82 pubmed publisher
    ..These relationships are consistent with our in vitro observations and indicate that TFAP2B seems to regulate the expression of various adipokines in vivo. ..
  47. Yuan P, Han J, Guo G, Orlov Y, Huss M, Loh Y, et al. Eset partners with Oct4 to restrict extraembryonic trophoblast lineage potential in embryonic stem cells. Genes Dev. 2009;23:2507-20 pubmed publisher
    ..Our results suggest that Eset restricts the extraembryonic trophoblast lineage potential of pluripotent cells and links an epigenetic regulator to key cell fate decision through a pluripotency factor. ..
  48. Weber S, Eckert D, Nettersheim D, Gillis A, Schäfer S, Kuckenberg P, et al. Critical function of AP-2 gamma/TCFAP2C in mouse embryonic germ cell maintenance. Biol Reprod. 2010;82:214-23 pubmed publisher
    ..Our results implicate Tcfap2c as an important effector of Prdm1 activity that is required for PGC maintenance, most likely mediating Prdm1-induced suppression of mesodermal differentiation. ..
  49. Kuckenberg P, Buhl S, Woynecki T, van Fürden B, Tolkunova E, Seiffe F, et al. The transcription factor TCFAP2C/AP-2gamma cooperates with CDX2 to maintain trophectoderm formation. Mol Cell Biol. 2010;30:3310-20 pubmed publisher
    ..Taken together, these observations suggest that Tcfap2c and Cdx2 cooperate to override the pluripotency program and establish the extraembryonic trophoblast maintenance program in murine embryos. ..
  50. Aas P, Pena Diaz J, Liabakk N, Krokan H, Skorpen F. Overexpression of transcription factor AP-2 stimulates the PA promoter of the human uracil-DNA glycosylase (UNG) gene through a mechanism involving derepression. DNA Repair (Amst). 2009;8:822-33 pubmed publisher
  51. Favilla V, Cimino S, Madonia M, Morgia G. New advances in clinical biomarkers in testis cancer. Front Biosci (Elite Ed). 2010;2:456-77 pubmed
    ..Further research is need in this context for the detection of new markers. ..
  52. Rao J, Rapoport S. Mood-stabilizers target the brain arachidonic acid cascade. Curr Mol Pharmacol. 2009;2:207-14 pubmed
    ..In this review, we discuss the mechanisms of action of mood stabilizers and the effects of docosahexaenoic acid on AA cascade enzymes in relation to BD. ..