Activation of the TFAP2 (AP-2) family of transcription factors

Stable Identifier
R-HSA-8866907
Type
Pathway
Species
Homo sapiens
Locations in the PathwayBrowser
Summation

The helix-span-helix motif and the basic region of TFAP2 (AP-2) transcription factor family members TFAP2A, TFAP2B, TFAP2C, TFAP2D and TFAP2E enable dimerization and DNA binding. AP-2 dimers bind palindromic GC-rich DNA response elements that match the consensus sequence 5'-GCCNNNGGC-3' (Williams and Tjian 1991a, Williams and Tjian 1991b). Most of the AP-2 binding sites slightly differ from the consensus, and individual AP-2 family members may differ in their binding site preferences (McPherson and Weigel 1999, Orso et al. 2010). Transcriptional co-factors from the CITED family interact with the helix-span-helix (HSH) domain of TFAP2 (AP-2) family of transcription factors and recruit transcription co-activators EP300 (p300) and CREBBP (CBP) to TFAP2-bound DNA elements. CITED2 shows the highest affinity for TFAP2 proteins, followed by CITED4, while CITED1 interacts with TFAP2s with a very low affinity. Mouse embryos defective for CITED2 exhibit neural crest defects, cardiac malformations and adrenal agenesis, which can at least in part be attributed to a defective Tfap2 transactivation (Bamforth et al. 2001, Braganca et al. 2002, Braganca et al. 2003). DNA binding and transcriptional activity of TFAP2B homodimers is increased by binding to YEATS4 (GAS41) (Ding et al. 2006).

Literature References
PubMed ID Title Journal Year
1998122 Characterization of a dimerization motif in AP-2 and its function in heterologous DNA-binding proteins

Williams, T, Tjian, R

Science 1991
11744733 Human CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) 4, a new member of the CITED family, functions as a co-activator for transcription factor AP-2

Braganša, J, Swingler, T, Marques, FI, Jones, T, Eloranta, JJ, Hurst, HC, Shioda, T, Bhattacharya, S

J. Biol. Chem. 2002
2010091 Analysis of the DNA-binding and activation properties of the human transcription factor AP-2

Williams, T, Tjian, R

Genes Dev. 1991
10497269 AP2alpha and AP2gamma: a comparison of binding site specificity and trans-activation of the estrogen receptor promoter and single site promoter constructs

McPherson, LA, Weigel, RJ

Nucleic Acids Res. 1999
11694877 Cardiac malformations, adrenal agenesis, neural crest defects and exencephaly in mice lacking Cited2, a new Tfap2 co-activator

Bamforth, SD, Braganša, J, Eloranta, JJ, Murdoch, JN, Marques, FI, Kranc, KR, Farza, H, Henderson, DJ, Hurst, HC, Bhattacharya, S

Nat. Genet. 2001
20525283 Identification of functional TFAP2A and SP1 binding sites in new TFAP2A-modulated genes

Orso, F, CorÓ, D, Ubezio, B, Provero, P, Caselle, M, Taverna, D

BMC Genomics 2010
12586840 Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2

Braganša, J, Eloranta, JJ, Bamforth, SD, Ibbitt, JC, Hurst, HC, Bhattacharya, S

J. Biol. Chem. 2003
16698963 GAS41 interacts with transcription factor AP-2beta and stimulates AP-2beta-mediated transactivation

Ding, X, Fan, C, Zhou, J, Zhong, Y, Liu, R, Ren, K, Hu, X, Luo, C, Xiao, S, Wang, Y, Feng, D, Zhang, J

Nucleic Acids Res. 2006
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