Gene Symbol: Tfap2a
Description: transcription factor AP-2 alpha
Alias: Tcfap2a, transcription factor AP-2-alpha, AP-2 transcription factor, AP2-alpha, activating enhancer-binding protein 2-alpha, activator protein 2
Species: rat
Products:     Tfap2a

Top Publications

  1. McPherson L, Loktev A, Weigel R. Tumor suppressor activity of AP2alpha mediated through a direct interaction with p53. J Biol Chem. 2002;277:45028-33 pubmed
    ..These results also provide a mechanism to explain patterns of gene expression in cancers where AP2alpha is known to function as a tumor suppressor. ..
  2. Nottoli T, Hagopian Donaldson S, Zhang J, Perkins A, Williams T. AP-2-null cells disrupt morphogenesis of the eye, face, and limbs in chimeric mice. Proc Natl Acad Sci U S A. 1998;95:13714-9 pubmed
  3. Bamforth S, Braganca J, Eloranta J, Murdoch J, Marques F, Kranc K, et al. Cardiac malformations, adrenal agenesis, neural crest defects and exencephaly in mice lacking Cited2, a new Tfap2 co-activator. Nat Genet. 2001;29:469-74 pubmed
    ..As certain Tfap2 isoforms are essential in neural crest, neural tube and cardiac development, we propose that abnormal embryogenesis in mice lacking Cited2 results, at least in part, from its role as a Tfap2 co-activator. ..
  4. Moser M, Imhof A, Pscherer A, Bauer R, Amselgruber W, Sinowatz F, et al. Cloning and characterization of a second AP-2 transcription factor: AP-2 beta. Development. 1995;121:2779-88 pubmed
    ..In summary, our analyses of embryonic and adult mice demonstrate that two different AP-2 transcription factors are specifically expressed during differentiation of many neural, epidermal and urogenital tissues. ..
  5. Brewer S, Jiang X, Donaldson S, Williams T, Sucov H. Requirement for AP-2alpha in cardiac outflow tract morphogenesis. Mech Dev. 2002;110:139-49 pubmed
    ..5. AP-2alpha may be involved in an interaction between neural crest and surrounding tissues in the subpharyngeal region, thereby promoting normal outflow tract morphogenesis. ..
  6. Kramer P, Krishnamurthy R, Mitchell P, Wray S. Transcription factor activator protein-2 is required for continued luteinizing hormone-releasing hormone expression in the forebrain of developing mice. Endocrinology. 2000;141:1823-38 pubmed
    ..These results indicate a developmentally restricted involvement of the transcription factor AP-2 in LHRH expression once the LHRH neurons have migrated into the forebrain, but before establishment of an adult-like distribution. ..
  7. Schorle H, Meier P, Buchert M, Jaenisch R, Mitchell P. Transcription factor AP-2 essential for cranial closure and craniofacial development. Nature. 1996;381:235-8 pubmed
  8. Zhang J, Hagopian Donaldson S, Serbedzija G, Elsemore J, Plehn Dujowich D, McMahon A, et al. Neural tube, skeletal and body wall defects in mice lacking transcription factor AP-2. Nature. 1996;381:238-41 pubmed
    ..Analysis of these mice earlier in embryogenesis indicates a failure of cranial neural-tube closure and defects in cranial ganglia development. We have shown that AP-2 is a fundamental regulator of mammalian craniofacial development. ..
  9. Talbot D, Loring J, Schorle H, Lorgin J. Spatiotemporal expression pattern of keratins in skin of AP-2alpha-deficient mice. J Invest Dermatol. 1999;113:816-20 pubmed
    ..Furthermore, the mutants lack a ring of ectodermal cells highly positive for keratin 15 in the area where lens induction occurs, indicating a defect in the inductive interactions underlying eye formation. ..

More Information


  1. Zhu C, Huang Y, Oberley L, Domann F. A family of AP-2 proteins down-regulate manganese superoxide dismutase expression. J Biol Chem. 2001;276:14407-13 pubmed
    ..These results indicate that AP-2-mediated transcriptional repression contributes to the constitutively low expression of Mn-SOD in SV40-transformed fibroblasts and suggest a mechanism for Mn-SOD down-regulation in cancer. ..
  2. Braganca J, Eloranta J, Bamforth S, Ibbitt J, Hurst H, Bhattacharya S. Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2. J Biol Chem. 2003;278:16021-9 pubmed
    ..p300/CBP, CITED2, and TFAP2A are essential for normal neural tube and cardiac development...
  3. Zhao F, Satoda M, Licht J, Hayashizaki Y, Gelb B. Cloning and characterization of a novel mouse AP-2 transcription factor, AP-2delta, with unique DNA binding and transactivation properties. J Biol Chem. 2001;276:40755-60 pubmed
    ..The unique protein sequence and functional features of Ap-2delta suggest mechanisms, besides tissue-specific AP-2 gene expression, for specific control of target gene activation. ..
  4. Li K, Singh A, Crooks D, Dai X, Cong Z, Pan L, et al. Expression of human frataxin is regulated by transcription factors SRF and TFAP2. PLoS ONE. 2010;5:e12286 pubmed publisher
    ..By providing new mechanistic insights into the molecular factors influencing frataxin expression, our results should aid in the discovery of new therapeutic targets for the treatment of Friedreich ataxia. ..
  5. Yu L, Hitchler M, Sun W, Sarsour E, Goswami P, Klingelhutz A, et al. AP-2alpha Inhibits c-MYC Induced Oxidative Stress and Apoptosis in HaCaT Human Keratinocytes. J Oncol. 2009;2009:780874 pubmed publisher
    ..The effects of AP-2 on c-MYC induced ROS accumulation and apoptosis in epidermal keratinocytes are likely to play an important role in cell growth, differentiation and carcinogenesis of the skin. ..
  6. Morales Lázaro S, González Ramírez R, Gomez P, Tapia Ramírez V, de León M, Cisneros B. Induction of dystrophin Dp71 expression during neuronal differentiation: opposite roles of Sp1 and AP2alpha in Dp71 promoter activity. J Neurochem. 2010;112:474-85 pubmed publisher
  7. Maconochie M, Krishnamurthy R, Nonchev S, Meier P, Manzanares M, Mitchell P, et al. Regulation of Hoxa2 in cranial neural crest cells involves members of the AP-2 family. Development. 1999;126:1483-94 pubmed
    ..Our findings have identified the cis-components that allow Hoxa2 to be regulated independently in rhombomeres and cranial neural crest cells. ..
  8. Borgonovo J, Capella P, Seltzer A, Sosa M. Expression of coat proteins changes during postnatal development in selected areas of the rat brain. Int J Dev Neurosci. 2012;30:333-41 pubmed publisher
    ..These results suggest that proteins that conform the intracellular transport machinery in the brain cells seems to accompany development, according to the maturation of the different brain areas. ..
  9. 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. ..
  10. West Mays J, Zhang J, Nottoli T, Hagopian Donaldson S, Libby D, Strissel K, et al. AP-2alpha transcription factor is required for early morphogenesis of the lens vesicle. Dev Biol. 1999;206:46-62 pubmed
    ..Together these findings demonstrate a requirement for AP-2alpha in early morphogenesis of the eye. ..
  11. Khomenko T, Deng X, Jadus M, Szabo S. Effect of cysteamine on redox-sensitive thiol-containing proteins in the duodenal mucosa. Biochem Biophys Res Commun. 2003;309:910-6 pubmed
    ..Thus, redox-sensitive signaling systems seem to play an important role in cysteamine-induced duodenal ulceration. ..
  12. Zhao F, Bosserhoff A, Buettner R, Moser M. A heart-hand syndrome gene: Tfap2b plays a critical role in the development and remodeling of mouse ductus arteriosus and limb patterning. PLoS ONE. 2011;6:e22908 pubmed publisher
    ..Loss of Tfap2b results in altered Bmp expression that may cause the heart-limb defects observed in Tfap2b mouse mutants and Char syndrome patients. The Tfap2b knockout mouse may add to the very limited available animal models of PDA. ..
  13. Ritter B, Denisov A, Philie J, Allaire P, Legendre Guillemin V, Zylbergold P, et al. The NECAP PHear domain increases clathrin accessory protein binding potential. EMBO J. 2007;26:4066-77 pubmed
    ..Our data uncover a striking convergence of two evolutionarily and structurally distinct modules to recognize a common peptide motif and promote efficient endocytosis. ..
  14. Duan C, Clemmons D. Transcription factor AP-2 regulates human insulin-like growth factor binding protein-5 gene expression. J Biol Chem. 1995;270:24844-51 pubmed
    ..This AP-2-mediated trans-activation contributes at least in part to the constitutively high expression of IGFBP-5 in fibroblasts and to the cAMP responsiveness of this gene. ..
  15. Adam C, Cyr D. Role of Specificity Protein-1 and Activating Protein-2 Transcription Factors in the Regulation of the Gap Junction Protein Beta-2 Gene in the Epididymis of the Rat. Biol Reprod. 2016;94:120 pubmed publisher
    ..Computational analysis revealed several TFAP2A, SP1, and KLF4 putative binding sites. A 1...
  16. Muller F, Loser K, Kleideiter U, Neumann J, von Wallbrunn C, Dobner T, et al. Transcription factor AP-2alpha triggers apoptosis in cardiac myocytes. Cell Death Differ. 2004;11:485-93 pubmed
    ..We suggest AP-2alpha as a novel cardiac regulator implicated in the activation of apoptosis in IDC. ..
  17. Li B, Kramer P, Zhao W, Ma W, Stenger D, Zhang L. Molecular cloning, expression, and characterization of rat homolog of human AP-2alpha that stimulates neuropeptide Y transcription activity in response to nerve growth factor. Mol Endocrinol. 2000;14:837-47 pubmed
  18. Damberg M, Ekblom J, Oreland L. Chronic pharmacological treatment with certain antidepressants alters the expression and DNA-binding activity of transcription factor AP-2. Life Sci. 2000;68:669-78 pubmed
    ..An increased understanding of the function of transcription factors and their involvement in human disease, such as depression, could make it possible in the future to selectively modulate relevant target genes directly. ..
  19. Buettner R, Kannan P, Imhof A, Bauer R, Yim S, Glockshuber R, et al. An alternatively spliced mRNA from the AP-2 gene encodes a negative regulator of transcriptional activation by AP-2. Mol Cell Biol. 1993;13:4174-85 pubmed
    ..Therefore, inhibition of AP-2 activity by the protein AP-2B may require an additional factor or modification supplied by nuclear extracts. ..
  20. 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. ..
  21. Eloranta J, Hurst H. Transcription factor AP-2 interacts with the SUMO-conjugating enzyme UBC9 and is sumolated in vivo. J Biol Chem. 2002;277:30798-804 pubmed
    ..Transient transfection studies indicate that sumolation of AP-2 decreases its transcription activation potential, and we discuss the possible mechanisms for the observed suppression of AP-2 transactivation. ..
  22. Imhof A, Schuierer M, Werner O, Moser M, Roth C, Bauer R, et al. Transcriptional regulation of the AP-2alpha promoter by BTEB-1 and AP-2rep, a novel wt-1/egr-related zinc finger repressor. Mol Cell Biol. 1999;19:194-204 pubmed
  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
    ..392?bp of promoter, containing early growth response protein (Egr-1), specificity protein 1 (Sp1) and activator protein 2 (AP-2) binding sites (-165, -168 and -103?bp, respectively), was sufficient for PACAP activation...
  24. 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. ..
  25. Meeker R, Fernandes A. Sustained increases in activating transcription factor-2 and activator protein-2 in the rat supraoptic nucleus during water deprivation. Neuroendocrinology. 2002;76:111-20 pubmed
  26. Dwivedi D, Pontoriero G, Ashery Padan R, Sullivan S, Williams T, West Mays J. Targeted deletion of AP-2alpha leads to disruption in corneal epithelial cell integrity and defects in the corneal stroma. Invest Ophthalmol Vis Sci. 2005;46:3623-30 pubmed
    ..In the absence of AP-2alpha, the corneal epithelium exhibits altered cell adhesion and integrity and defects in its underlying basement membrane. These defects likely caused the alterations in the corneal stroma. ..
  27. Henne W, Boucrot E, Meinecke M, Evergren E, Vallis Y, Mittal R, et al. FCHo proteins are nucleators of clathrin-mediated endocytosis. Science. 2010;328:1281-4 pubmed publisher
    ..The FCHo F-BAR membrane-bending activity was required, leading to the proposal that FCHo1/2 sculpt the initial bud site and recruit the clathrin machinery for CCV formation. ..
  28. Ye X, Liu S. Lipopolysaccharide regulates constitutive and inducible transcription factor activities differentially in vivo in the rat. Biochem Biophys Res Commun. 2001;288:927-32 pubmed
    ..Thus, LPS regulates the inducible and constitutive transcription factors differentially under in vivo conditions. ..
  29. Milunsky J, Maher T, Zhao G, Wang Z, Mulliken J, Chitayat D, et al. Genotype-phenotype analysis of the branchio-oculo-facial syndrome. Am J Med Genet A. 2011;155A:22-32 pubmed publisher
    ..Having determined that mutations involving TFAP2A result in BOFS, we studied a total of 30 families (41 affected individuals); 26/30 (87%) fulfilled our cardinal ..
  30. Kramer P, Guerrero G, Krishnamurthy R, Mitchell P, Wray S. Ectopic expression of luteinizing hormone-releasing hormone and peripherin in the respiratory epithelium of mice lacking transcription factor AP-2alpha. Mech Dev. 2000;94:79-94 pubmed
  31. Bamforth S, Braganca J, Farthing C, Schneider J, Broadbent C, Michell A, et al. Cited2 controls left-right patterning and heart development through a Nodal-Pitx2c pathway. Nat Genet. 2004;36:1189-96 pubmed
    ..We propose that an abnormal Nodal-Pitx2c pathway represents a unifying mechanism for the cardiovascular malformations observed in Cited2(-/-) mice, and that such malformations may be the sole manifestation of a laterality defect. ..
  32. Lin H, Chen Y, Chiang M, Huang P, Chau L. Activator protein-2? mediates carbon monoxide-induced stromal cell-derived factor-1? expression and vascularization in ischemic heart. Arterioscler Thromb Vasc Biol. 2013;33:785-94 pubmed publisher
    ..assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation demonstrated that the activator protein 2? (AP-2?) mediated tricarbonyldichlororuthenium (II) dimer-induced SDF-1? gene transcription...
  33. Stewart H, Brennan A, Rahman M, Zoidl G, Mitchell P, Jessen K, et al. Developmental regulation and overexpression of the transcription factor AP-2, a potential regulator of the timing of Schwann cell generation. Eur J Neurosci. 2001;14:363-72 pubmed
    ..Moreover, Schwann cell generation was delayed if this downregulation was prevented by enforced expression of AP-2 alpha in precursors. These studies suggest that AP-2 is involved in the control of the timing of Schwann cell development. ..
  34. 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
    ..Our previous work has suggested that transcription factor activating protein-2 alpha (AP-2alpha; Tcfap2a) has a non-cell autonomous role in optic cup (OC) development; however, it remained unclear how OC abnormalities ..
  35. Lokeshwar V, Gomez P, Kramer M, Knapp J, McCornack M, Lopez L, et al. Epigenetic regulation of HYAL-1 hyaluronidase expression. identification of HYAL-1 promoter. J Biol Chem. 2008;283:29215-27 pubmed publisher
    ..Thus, HYAL-1 expression is epigenetically regulated by the binding of different transcription factors to the methylated and unmethylated HYAL-1 promoter. ..
  36. Pontoriero G, Deschamps P, Ashery Padan R, Wong R, Yang Y, Zavadil J, et al. Cell autonomous roles for AP-2alpha in lens vesicle separation and maintenance of the lens epithelial cell phenotype. Dev Dyn. 2008;237:602-17 pubmed publisher
    ..wild-type littermates revealed differential expression of 415 mRNAs, including reduced expression of genes important for maintaining the lens epithelial cell phenotype, such as E-cadherin. ..
  37. Wang X, Bolotin D, Chu D, Polak L, Williams T, Fuchs E. AP-2alpha: a regulator of EGF receptor signaling and proliferation in skin epidermis. J Cell Biol. 2006;172:409-21 pubmed
    ..These results provide insights into why elevated AP-2alpha levels are often associated with terminal differentiation and why tumor cells often display reduced AP-2alpha and elevated EGFR proteins. ..
  38. Brewer S, Williams T. Loss of AP-2alpha impacts multiple aspects of ventral body wall development and closure. Dev Biol. 2004;267:399-417 pubmed
    ..These findings provide a fundamental understanding of how AP-2alpha functions in the closure of the ventral body wall, as well as offer insight into related human birth defects. ..
  39. Li X, Glubrecht D, Godbout R. AP2 transcription factor induces apoptosis in retinoblastoma cells. Genes Chromosomes Cancer. 2010;49:819-30 pubmed publisher
    ..The RB protein has previously been shown to interact with TFAP2 transcription factors. Here, we show that TFAP2A and TFAP2B, which map to chromosome arm 6p, are expressed in the amacrine and horizontal cells of human retina...
  40. Ding X, Luo C, Zhou J, Zhong Y, Hu X, Zhou F, et al. The interaction of KCTD1 with transcription factor AP-2alpha inhibits its transactivation. J Cell Biochem. 2009;106:285-95 pubmed publisher
    ..Taken together, our results indicate the novel function of KCTD1 as the transcriptional repressor for AP-2 family, especially for AP-2alpha. ..
  41. Schmidt M, Huber L, Majdazari A, Schutz G, Williams T, Rohrer H. The transcription factors AP-2? and AP-2? are required for survival of sympathetic progenitors and differentiated sympathetic neurons. Dev Biol. 2011;355:89-100 pubmed publisher
    ..Whereas AP-2?/? transcription factors are in vivo not required for the onset or maintenance of noradrenergic differentiation, their essential survival functions are demonstrated for sympathetic progenitors and noradrenergic neurons. ..
  42. Jiang M, Tang Q, McLenithan J, Geiman D, Shillinglaw W, Henzel W, et al. Derepression of the C/EBPalpha gene during adipogenesis: identification of AP-2alpha as a repressor. Proc Natl Acad Sci U S A. 1998;95:3467-71 pubmed
    ..Taken together with previous results, these findings suggest that in preadipocytes the C/EBPalpha gene is repressed by AP-2alpha/CUP, which, upon induction of differentiation, is down-regulated, allowing expression of the gene. ..
  43. Feng W, Huang J, Zhang J, Williams T. Identification and analysis of a conserved Tcfap2a intronic enhancer element required for expression in facial and limb bud mesenchyme. Mol Cell Biol. 2008;28:315-25 pubmed
    b>Tcfap2a, the gene encoding the mouse AP-2alpha transcription factor, is required for normal development of multiple structures during embryogenesis, including the face and limbs...
  44. Fan Z, Yamaza T, Lee J, Yu J, Wang S, Fan G, et al. BCOR regulates mesenchymal stem cell function by epigenetic mechanisms. Nat Cell Biol. 2009;11:1002-9 pubmed publisher
    ..By studying a rare human genetic disease, we have unravelled an epigenetic mechanism for control of human adult stem cell function. ..
  45. Scibetta A, Wong P, Chan K, Canosa M, Hurst H. Dual association by TFAP2A during activation of the p21cip/CDKN1A promoter. Cell Cycle. 2010;9:4525-32 pubmed
    ..factors with tumour suppressor activity can also regulate CDKN1A, including the developmentally regulated factor, TFAP2A. Here we identify a novel AP-2 binding site within the proximal promoter of the CDKN1A gene and show this is ..