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TFAP2A  -  transcription factor AP-2 alpha...

Homo sapiens

 
 
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Disease relevance of TFAP2A

  • Activator protein-2 overexpression accounts for increased insulin receptor expression in human breast cancer [1].
  • In this study, we have made a replication-deficient recombinant adenovirus that expresses functional AP-2alpha (Ad-AP2) [2].
  • Together, these results support a model in which HIV-1 Nef downregulates CD4 by promoting its accelerated endocytosis by a clathrin/AP2 pathway [3].
  • The purpose of our study was to determine AP-2alpha expression distribution among grades of gliomas and any possible effect on prognosis [4].
  • Adjacent to this region in HHV-6 are approximately 30 copies of a 103- to 108-bp sequence element, which contains consensus binding sites for the transcription factors AP2 and NF kappa B, in addition to a single KpnI recognition site [5].
 

Psychiatry related information on TFAP2A

  • Sp1 and AP2 transcription factors are required for the human fragile mental retardation promoter activity in SK-N-SH neuronal cells [6].
  • Clathrin assembly protein AP-2 is detected in both neurons and glia, and its reduction is prominent in layer II of frontal cortex in Alzheimer's disease [7].
 

High impact information on TFAP2A

  • Binding of clathrin AP-2 (adaptor complex) to an unidentified high affinity membrane receptor appears to be necessary for coated pit assembly in fibroblasts [8].
  • We now show that synaptic vesicles have a high affinity AP-2 site (KD, approximately 1 x 10(-10) M) similar to the one observed in fibroblasts [8].
  • Multiple synthetic copies of the hMT-IIA high-affinity AP-2 binding site can act as efficient, cell-type-specific enhancer elements; their activity increases after treatment of cells with phorbol ester or cAMP-elevating agents [9].
  • AP-2 appears to mediate transcriptional activation in response to two different signal-transduction pathways, one involving the phorbol-ester- and diacylglycerol-activated protein kinase C, the other involving cAMP-dependent protein kinase A [9].
  • Juxtaposed binding sites for AP-2 and Sp1 in the 21 bp repeats may facilitate productive interactions between the two factors [10].
 

Chemical compound and disease context of TFAP2A

 

Biological context of TFAP2A

 

Anatomical context of TFAP2A

 

Associations of TFAP2A with chemical compounds

 

Physical interactions of TFAP2A

  • A highly conserved 20-amino acid sequence in the C-terminal region of ARH bound the beta(2)-adaptin subunit of AP-2 [27].
  • In mammalian two-hybrid experiments, full-length p300 and TFAP2A interacted only when CITED2 was co-transfected [16].
  • Candidate p53-binding sites were identified in the AP-2alpha and AP-2gamma promoters. p53 binding to these cis-elements in vivo was also observed, together with a relaxation of chromatin structure in these regions [28].
  • In vitro studies using coimmunoprecipitation experiments and a yeast three-hybrid assay reveal that c-Src stabilizes the agonist-independent association between beta-arrestin2 and the beta-subunit of AP-2 independently of the kinase activity of c-Src [19].
  • We examined the contribution of the new AP-2 binding site to ERBB2 overexpression [29].
 

Regulatory relationships of TFAP2A

  • Furthermore, we demonstrated that AP-2alpha directly interacted with Sp1 to form transcription complexes at two tandem Sp1-binding sites of the promoter to activate KiSS-1 transcription [30].
  • The human reduced folate carrier gene is regulated by the AP2 and sp1 transcription factor families and a functional 61-base pair polymorphism [31].
  • Thus, the consequence of c-Src in regulating the dissociation of AP-2 from the receptor was also examined on the internalization of AT1R by depleting c-Src in human embryonic kidney (HEK) 293 cells using a small interfering RNA strategy [19].
  • Inefficient proteasomal-degradation pathway stabilizes AP-2alpha and activates HER-2/neu gene in breast cancer [21].
  • These results demonstrate that AP2 can activate EGF receptor gene expression and may mediate the PMA response of this gene [32].
 

Other interactions of TFAP2A

  • VEGF expression is controlled by the transcription factors activator protein (AP)-1, AP-2, SP-1, and hypoxia-inducible factor 1 [33].
  • Our findings support this hypothesis and suggest that in affected individuals, hyperactivation of the AP-2 gene through the overexpression of IR may play a key role in breast carcinogenesis [1].
  • Overexpression of AP-2alpha into highly metastatic breast cell lines did not alter KiSS-1 promoter-driven luciferase gene activity [30].
  • ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2 [27].
  • Strikingly, approximately 80% of the cell lines displayed a simultaneously decreased binding to three or more of these hRFC promoter elements, whereas normal AP-2 binding was retained [34].
 

Analytical, diagnostic and therapeutic context of TFAP2A

References

  1. Activator protein-2 overexpression accounts for increased insulin receptor expression in human breast cancer. Paonessa, F., Foti, D., Costa, V., Chiefari, E., Brunetti, G., Leone, F., Luciano, F., Wu, F., Lee, A.S., Gulletta, E., Fusco, A., Brunetti, A. Cancer Res. (2006) [Pubmed]
  2. Cell cycle arrest and apoptosis induction by activator protein 2alpha (AP-2alpha) and the role of p53 and p21WAF1/CIP1 in AP-2alpha-mediated growth inhibition. Wajapeyee, N., Somasundaram, K. J. Biol. Chem. (2003) [Pubmed]
  3. Downregulation of CD4 by human immunodeficiency virus type 1 nef is dependent on clathrin and involves direct interaction of nef with the AP2 clathrin adaptor. Chaudhuri, R., Lindwasser, O.W., Smith, W.J., Hurley, J.H., Bonifacino, J.S. J. Virol. (2007) [Pubmed]
  4. Loss of the AP-2alpha transcription factor is associated with the grade of human gliomas. Heimberger, A.B., McGary, E.C., Suki, D., Ruiz, M., Wang, H., Fuller, G.N., Bar-Eli, M. Clin. Cancer Res. (2005) [Pubmed]
  5. Identification of a transactivating function mapping to the putative immediate-early locus of human herpesvirus 6. Martin, M.E., Nicholas, J., Thomson, B.J., Newman, C., Honess, R.W. J. Virol. (1991) [Pubmed]
  6. Sp1 and AP2 transcription factors are required for the human fragile mental retardation promoter activity in SK-N-SH neuronal cells. Carrillo, C., Cisneros, B., Montañez, C. Neurosci. Lett. (1999) [Pubmed]
  7. Clathrin assembly protein AP-2 is detected in both neurons and glia, and its reduction is prominent in layer II of frontal cortex in Alzheimer's disease. Yao, P.J., Weimer, J.M., O'Herron, T.M., Coleman, P.D. Neurobiol. Aging (2000) [Pubmed]
  8. Synaptotagmin I is a high affinity receptor for clathrin AP-2: implications for membrane recycling. Zhang, J.Z., Davletov, B.A., Südhof, T.C., Anderson, R.G. Cell (1994) [Pubmed]
  9. Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP. Imagawa, M., Chiu, R., Karin, M. Cell (1987) [Pubmed]
  10. Positive and negative regulation of transcription in vitro: enhancer-binding protein AP-2 is inhibited by SV40 T antigen. Mitchell, P.J., Wang, C., Tjian, R. Cell (1987) [Pubmed]
  11. Activator protein 2alpha status determines the chemosensitivity of cancer cells: implications in cancer chemotherapy. Wajapeyee, N., Raut, C.G., Somasundaram, K. Cancer Res. (2005) [Pubmed]
  12. Activator protein 2alpha transcription factor expression is associated with luminal differentiation and is lost in prostate cancer. Ruiz, M., Troncoso, P., Bruns, C., Bar-Eli, M. Clin. Cancer Res. (2001) [Pubmed]
  13. Sleep apnea impairs the arousal response to airway occlusion. Berry, R.B., Kouchi, K.G., Der, D.E., Dickel, M.J., Light, R.W. Chest (1996) [Pubmed]
  14. Experimental study of anti-tumor effects of polysaccharides from Angelica sinensis. Shang, P., Qian, A.R., Yang, T.H., Jia, M., Mei, Q.B., Cho, C.H., Zhao, W.M., Chen, Z.N. World J. Gastroenterol. (2003) [Pubmed]
  15. A region from the medium chain adaptor subunit (mu) recognizes leucine- and tyrosine-based sorting signals. Bremnes, T., Lauvrak, V., Lindqvist, B., Bakke, O. J. Biol. Chem. (1998) [Pubmed]
  16. Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2. Bragança, J., Eloranta, J.J., Bamforth, S.D., Ibbitt, J.C., Hurst, H.C., Bhattacharya, S. J. Biol. Chem. (2003) [Pubmed]
  17. AP-2alpha selectively regulates fragile X mental retardation-1 gene transcription during embryonic development. Lim, J.H., Booker, A.B., Luo, T., Williams, T., Furuta, Y., Lagutin, O., Oliver, G., Sargent, T.D., Fallon, J.R. Hum. Mol. Genet. (2005) [Pubmed]
  18. Expression of AP-2 transcription factors in human breast cancer correlates with the regulation of multiple growth factor signalling pathways. Turner, B.C., Zhang, J., Gumbs, A.A., Maher, M.G., Kaplan, L., Carter, D., Glazer, P.M., Hurst, H.C., Haffty, B.G., Williams, T. Cancer Res. (1998) [Pubmed]
  19. c-Src regulates clathrin adapter protein 2 interaction with beta-arrestin and the angiotensin II type 1 receptor during clathrin- mediated internalization. Fessart, D., Simaan, M., Laporte, S.A. Mol. Endocrinol. (2005) [Pubmed]
  20. Essential role of an activator protein-2 (AP-2)/specificity protein 1 (Sp1) cluster in the UVB-mediated induction of the human vascular endothelial growth factor in HaCaT keratinocytes. Brenneisen, P., Blaudschun, R., Gille, J., Schneider, L., Hinrichs, R., Wlaschek, M., Eming, S., Scharffetter-Kochanek, K. Biochem. J. (2003) [Pubmed]
  21. Inefficient proteasomal-degradation pathway stabilizes AP-2alpha and activates HER-2/neu gene in breast cancer. Li, M., Wang, Y., Hung, M.C., Kannan, P. Int. J. Cancer (2006) [Pubmed]
  22. Tumor suppressor activity of AP2alpha mediated through a direct interaction with p53. McPherson, L.A., Loktev, A.V., Weigel, R.J. J. Biol. Chem. (2002) [Pubmed]
  23. The modular adaptor protein autosomal recessive hypercholesterolemia (ARH) promotes low density lipoprotein receptor clustering into clathrin-coated pits. Garuti, R., Jones, C., Li, W.P., Michaely, P., Herz, J., Gerard, R.D., Cohen, J.C., Hobbs, H.H. J. Biol. Chem. (2005) [Pubmed]
  24. Analysis of the DNA-binding and activation properties of the human transcription factor AP-2. Williams, T., Tjian, R. Genes Dev. (1991) [Pubmed]
  25. An alternatively spliced mRNA from the AP-2 gene encodes a negative regulator of transcriptional activation by AP-2. Buettner, R., Kannan, P., Imhof, A., Bauer, R., Yim, S.O., Glockshuber, R., Van Dyke, M.W., Tainsky, M.A. Mol. Cell. Biol. (1993) [Pubmed]
  26. The retinoblastoma protein binds the promoter of the survival gene bcl-2 and regulates its transcription in epithelial cells through transcription factor AP-2. Decary, S., Decesse, J.T., Ogryzko, V., Reed, J.C., Naguibneva, I., Harel-Bellan, A., Cremisi, C.E. Mol. Cell. Biol. (2002) [Pubmed]
  27. ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2. He, G., Gupta, S., Yi, M., Michaely, P., Hobbs, H.H., Cohen, J.C. J. Biol. Chem. (2002) [Pubmed]
  28. AP-2alpha and AP-2gamma are transcriptional targets of p53 in human breast carcinoma cells. Li, H., Watts, G.S., Oshiro, M.M., Futscher, B.W., Domann, F.E. Oncogene (2006) [Pubmed]
  29. Identification of HTF (HER2 transcription factor) as an AP-2 (activator protein-2) transcription factor and contribution of the HTF binding site to ERBB2 gene overexpression. Vernimmen, D., Begon, D., Salvador, C., Gofflot, S., Grooteclaes, M., Winkler, R. Biochem. J. (2003) [Pubmed]
  30. Regulation of KiSS-1 metastasis suppressor gene expression in breast cancer cells by direct interaction of transcription factors activator protein-2alpha and specificity protein-1. Mitchell, D.C., Abdelrahim, M., Weng, J., Stafford, L.J., Safe, S., Bar-Eli, M., Liu, M. J. Biol. Chem. (2006) [Pubmed]
  31. The human reduced folate carrier gene is regulated by the AP2 and sp1 transcription factor families and a functional 61-base pair polymorphism. Whetstine, J.R., Witt, T.L., Matherly, L.H. J. Biol. Chem. (2002) [Pubmed]
  32. Activation of epidermal growth factor receptor gene transcription by phorbol 12-myristate 13-acetate is mediated by activator protein 2. Johnson, A.C. J. Biol. Chem. (1996) [Pubmed]
  33. The constitutive photomorphogenesis 9 signalosome directs vascular endothelial growth factor production in tumor cells. Pollmann, C., Huang, X., Mall, J., Bech-Otschir, D., Naumann, M., Dubiel, W. Cancer Res. (2001) [Pubmed]
  34. Reduced folate carrier gene silencing in multiple antifolate-resistant tumor cell lines is due to a simultaneous loss of function of multiple transcription factors but not promoter methylation. Rothem, L., Stark, M., Kaufman, Y., Mayo, L., Assaraf, Y.G. J. Biol. Chem. (2004) [Pubmed]
  35. Functional dissection of an AP-2 beta2 appendage-binding sequence within the autosomal recessive hypercholesterolemia protein. Mishra, S.K., Keyel, P.A., Edeling, M.A., Dupin, A.L., Owen, D.J., Traub, L.M. J. Biol. Chem. (2005) [Pubmed]
 
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