Disease relevance of TFAP2B

• Mutations in TFAP2B cause Char syndrome, a familial form of patent ductus arteriosus [1].
• Genetic variations in the gene encoding TFAP2B are associated with type 2 diabetes mellitus [2].
• In an experiment using adenovirus vectors encoding TFAP2B, the expression of TNF-alpha gene was shown to be elevated in the TFAP2B overexpressing cells compared with those in control cells [3].
• We have cloned an alternative AP-2 transcript (AP-2B) from the human teratocarcinoma cell line PA-1, which encodes a protein differing in the C terminus from the previously isolated AP-2 protein (AP-2A) [4].
• Stable transfection of primary cutaneous melanoma SB-2 cells with the dominant-negative AP-2B gene was confirmed by RT--PCR and Northern blot analyses [5].

High impact information on TFAP2B

• Dimerization of both mutants with normal TFAP2B adversely affected transactivation, demonstrating a dominant-negative mechanism [1].
• Using a positional candidacy strategy, we mapped TFAP2B, encoding a transcription factor expressed in neural crest cells, to the Char syndrome critical region and identified missense mutations altering conserved residues in two affected families [1].
• Sequencing of TFAP2B demonstrated mutations in both kindreds that were not found among control chromosomes [6].
• Examination of these two kindreds for phenotypes that segregate with TFAP2B mutations identified several phenotypes not previously linked to Char syndrome [6].
• Both transient and stable transfection experiments show that AP-2B inhibits AP-2 transactivator function, as measured by an AP-2-responsive chloramphenicol acetyltransferase reporter plasmid [4].

Biological context of TFAP2B

• Investigation of transcription factor AP-2 beta genotype in women with premenstrual dysphoric disorder [7].
• We have identified a gene encoding transcription factor activating enhancer binding protein-2beta (TFAP2B) as a candidate for conferring susceptibility to type 2 diabetes [3].
• Intronic Polymorphisms within TFAP2B Regulate Transcriptional Activity and Affect Adipocytokine Gene Expression in Differentiated Adipocytes [3].
• Furthermore, we demonstrated that the expression of TFAP2B was increased in the adipose tissues of subjects with the disease-susceptibility allele, and the plasma levels of TNF-alpha and high sensitivity C-reactive peptide were significantly elevated in the patients with the disease-susceptibility allele [3].
• Recent analyses of autosomal dominant Char syndrome, which includes, with variable penetrance, patent ductus arteriosus as well as craniofacial and hand malformations, have shown that the syndrome is caused by mutations in the TFAP2B transcription factor gene [8].

Anatomical context of TFAP2B

• AP-2 alpha and AP-2 beta signals in the central and peripheral nervous system overlapped with regions of developing sensory neurons [9].
• Pigmented peripheral nerve sheath tumor of the oral cavity with expression of AP-2 beta and c-RET: a case report [10].

Associations of TFAP2B with chemical compounds

• Furthermore, constitutive AP-2B expression in PA-1 cells causes a retinoic acid-resistant phenotype, anchorage-independent growth in soft agar, and tumorigenicity in nude mice, in a fashion similar to transformation of these cells by oncogenes [4].
• However, small sample sizes from 1999-2003 for fish <1000 g limited the power of this comparison in Char and Amituk Lakes. In Resolute Lake char, manganese, strontium and zinc showed consistent decreases from 1997 or 1999 to 2003 while nickel generally increased over the 6 year period [11].
• Predominance of Char Sorption over Substrate Concentration and Soil pH in Influencing Biodegradation of Benzonitrile [12].
• Mean (+/- SD) Qm's (mg cholesterol adsorbed/gm dry sorbent) decreased in the order Super Char highly activated charcoal (277 +/- 121), Norit USP XX charcoal (33 +/- 10), Acta-Char charcoal (26 +/- 4), Mallinckrodt USP charcoal (26 +/- 10), Norit A charcoal (22 +/- 4) and cholestyramine (0) [13].

Other interactions of TFAP2B

• Therefore, inhibition of AP-2 activity by the protein AP-2B may require an additional factor or modification supplied by nuclear extracts [4].
• Expression of AP-2B in SB-2 cells augmented their tumorigenicity in nude mice, and upregulated MMP-2 expression and activity [14].
• Gel shift and supershift experiments supported binding of p53, junB and heterodimers of AP2alpha/AP2gamma or AP2beta/AP2gamma to this sequence [15].

Analytical, diagnostic and therapeutic context of TFAP2B

• We discuss differential diagnoses such as Setleis, Char and Lacrimo-Auriculo-Dento-Digital (LADD) syndromes [16].

References