TFAP2C explained

Transcription factor AP-2 gamma also known as AP2-gamma is a protein that in humans is encoded by the TFAP2C gene.^[1] AP2-gamma is a member of the activating protein 2 family of transcription factors.

Transcription factor AP-2 gamma is involved in early development, specifically morphogenesis - the formation of shape. AP2-gamma can regulate gene transcription by interacting with viral and cellular enhancing components and binding to the sequence 5'-GCCNNNGGC-3’. AP2-gamma activates genes that are important for placenta development and retinoic acid-mediated differentiation of the eyes, face, body wall, limbs, and neural tube. AP2-gamma also suppresses genes such as MYC and C/EBP alpha. It also represses CD44 expression, which is a cell marker for some breast and prostate cancers. Mutations of this transcription factor can lead to poorly developed placenta and tissues. A mutated AP2-gamma gene is known to cause branchiooculofacial syndrome (BOFS), which is a disease characterized by face and neck abnormalities, such as cleft lip or anophthalmia – lack of eyeballs, that have developed prior to birth. Complete knockout of the TAP2C gene that encoded AP-2 gamma leads to placenta malformation and embryonic/fetal death.

References

Auman, H. J., T. Nottoli, O. Lakiza, Q. Winger, S. Donaldson, and T. Williams. "Transcription Factor AP-2gamma Is Essential in the Extra-embryonic Lineages for Early Postimplantation Development." National Center for Biotechnology Information. U.S. National Library of Medicine, June 2002. Web. 15 Apr. 2014.

Bogachek, M. V., and R. J. Weigel. "TFAP2C (transcription Factor AP-2 Gamma (activating Enhancer Binding Protein 2 Gamma))." TFAP2C (transcription Factor AP-2 Gamma(activating Enhancer Binding Protein 2 Gamma)). Oct. 2013. Web. 15 Apr. 2014.

"Branchio-oculo-facial Syndrome." Genetics Home Reference. U.S. National Library of Medicine, 7 Apr. 2014. Web. 15 Apr. 2014.

"Genes and Mapped Phenotypes." National Center for Biotechnology Information. U.S. National Library of Medicine, 12 Apr. 2014. Web. 15 Apr. 2014.

"Transcription Factor AP-2 Gamma - TFAP2C - Homo sapiens (Human)." Transcription Factor AP-2 Gamma - TFAP2C - Homo sapiens (Human). UniProtKB, 19 Mar. 2014. Web. 15 Apr. 2014.

Further reading

• Pauls K, Jäger R, Weber S, etal . Transcription factor AP-2gamma, a novel marker of gonocytes and seminomatous germ cell tumors. . Int. J. Cancer . 115 . 3 . 470–7 . 2005 . 15700319 . 10.1002/ijc.20913 . 23301489 . free .
• Aqeilan RI, Palamarchuk A, Weigel RJ, etal . Physical and functional interactions between the Wwox tumor suppressor protein and the AP-2gamma transcription factor. . Cancer Res. . 64 . 22 . 8256–61 . 2004 . 15548692 . 10.1158/0008-5472.CAN-04-2055 . free .
• Woodfield GW, Hitchler MJ, Chen Y, etal . Interaction of TFAP2C with the estrogen receptor-alpha promoter is controlled by chromatin structure. . Clin. Cancer Res. . 15 . 11 . 3672–9 . 2009 . 19458056 . 10.1158/1078-0432.CCR-08-2343 . 2776721 .
• Williams CM, Scibetta AG, Friedrich JK, etal . AP-2gamma promotes proliferation in breast tumour cells by direct repression of the CDKN1A gene. . EMBO J. . 28 . 22 . 3591–601 . 2009 . 19798054 . 10.1038/emboj.2009.290 . 2782101 .
• Orso F, Penna E, Cimino D, etal . AP-2alpha and AP-2gamma regulate tumor progression via specific genetic programs. . FASEB J. . 22 . 8 . 2702–14 . 2008 . 18443366 . 10.1096/fj.08-106492 . free . 6531051 .
• Li H, Watts GS, Oshiro MM, etal . AP-2alpha and AP-2gamma are transcriptional targets of p53 in human breast carcinoma cells. . Oncogene . 25 . 39 . 5405–15 . 2006 . 16636674 . 10.1038/sj.onc.1209534 . free .
• Zhao C, Yasui K, Lee CJ, etal . Elevated expression levels of NCOA3, TOP1, and TFAP2C in breast tumors as predictors of poor prognosis. . Cancer . 98 . 1 . 18–23 . 2003 . 12833450 . 10.1002/cncr.11482 . 41092143 .
• Pellikainen JM, Ropponen KM, Kataja VV, etal . Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis. . Clin. Cancer Res. . 10 . 22 . 7621–8 . 2004 . 15569994 . 10.1158/1078-0432.CCR-04-1061 . free .
• Woodfield GW, Horan AD, Chen Y, Weigel RJ . TFAP2C controls hormone response in breast cancer cells through multiple pathways of estrogen signaling. . Cancer Res. . 67 . 18 . 8439–43 . 2007 . 17875680 . 10.1158/0008-5472.CAN-07-2293 . free .
• Bragança J, Eloranta JJ, Bamforth SD . Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2. . J. Biol. Chem. . 278 . 18 . 16021–9 . 2003 . 12586840 . 10.1074/jbc.M208144200 . etal. free .
• Friedrichs N, Steiner S, Buettner R, Knoepfle G . Immunohistochemical expression patterns of AP2alpha and AP2gamma in the developing fetal human breast. . Histopathology . 51 . 6 . 814–23 . 2007 . 18042070 . 10.1111/j.1365-2559.2007.02887.x . 85866319 .
• Li H, Goswami PC, Domann FE . AP-2gamma induces p21 expression, arrests cell cycle, and inhibits the tumor growth of human carcinoma cells. . Neoplasia . 8 . 7 . 568–77 . 2006 . 16867219 . 10.1593/neo.06367 . 1601932 .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Li M, Kellems RE . Sp1 and Sp3 Are important regulators of AP-2gamma gene transcription. . Biol. Reprod. . 69 . 4 . 1220–30 . 2003 . 12801994 . 10.1095/biolreprod.103.015545 . free .
• Orso F, Cottone E, Hasleton MD, etal . Activator protein-2gamma (AP-2gamma) expression is specifically induced by oestrogens through binding of the oestrogen receptor to a canonical element within the 5'-untranslated region. . Biochem. J. . 377 . Pt 2 . 429–38 . 2004 . 14565844 . 10.1042/BJ20031133 . 1223884 .
• Guler G, Huebner K, Himmetoglu C, etal . Fragile histidine triad protein, WW domain-containing oxidoreductase protein Wwox, and activator protein 2gamma expression levels correlate with basal phenotype in breast cancer. . Cancer . 115 . 4 . 899–908 . 2009 . 19130459 . 10.1002/cncr.24103 . 2640223 .
• Guler G, Iliopoulos D, Guler N, etal . Wwox and Ap2gamma expression levels predict tamoxifen response. . Clin. Cancer Res. . 13 . 20 . 6115–21 . 2007 . 17947476 . 10.1158/1078-0432.CCR-07-1282 . free .
• Kotani T, Iwase A, Ino K, etal . Activator protein-2 impairs the invasion of a human extravillous trophoblast cell line. . Endocrinology . 150 . 9 . 4376–85 . 2009 . 19443578 . 10.1210/en.2008-1645 . free .
• Ailan H, Xiangwen X, Daolong R, etal . Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells. . BMC Cancer . 9. 279 . 2009 . 19671168 . 10.1186/1471-2407-9-279 . 3224728 . free .

Notes and References

1. Williamson JA, Bosher JM, Skinner A, Sheer D, Williams T, Hurst HC . Chromosomal mapping of the human and mouse homologues of two new members of the AP-2 family of transcription factors . Genomics . 35 . 1 . 262–4 . July 1996 . 8661133 . 10.1006/geno.1996.0351 . free .