Disease relevance of TCF20

• A functional consequence is that SPBP inhibits the proliferation of ERalpha-dependent but not ERalpha-independent breast cancer cell lines, mirroring a reported negative correlation with the ERalpha status of breast tumors [1].
• We performed a phage display screen for human proteins that are exclusively recruited to the phosphorylated form of AF1 and found the stromelysin-1 platelet-derived growth factor-responsive element-binding protein (SPBP) [1].
• AR1 is an integral part of the adenovirus type 2 E1A-CR3 transactivation domain [2].
• The recombinant AR1 and AR2 proteins produced using a baculovirus expression system showed similar Km values for Cyt c and NADPH, respectively [3].
• Strain AR1 (group A, M-type 1) and G148 (group G), with strong immunoglobulin G (IgG) binding capacities, and strain AW43 (group A, M-type 60), binding both IgA1 and IgA2, were compared with Staphylococcus aureus Cowan I and with Staphylococcus epidermidis L603 [4].

High impact information on TCF20

• Functionally, SPBP behaved as a repressor of activated ERalpha, which extends its previously demonstrated roles as a DNA binding transactivation factor and coactivator of other transcription factors [1].
• In a purified system, SPBP bound only the in vitro-phosphorylated form of the ERalpha AF1 or the phosphoserine mimic S118E, and the interaction domain could be mapped to a 42-amino-acid fragment of SPBP [1].
• SPBP is a phosphoserine-specific repressor of estrogen receptor alpha [1].
• The 23-bp oligonucleotide designated AR1 from within the IL-6 enhancer region (-173 to -151) contains a CGTCA motif and bound nuclear proteins that also associated with c-fos oligonucleotides containing either an intact SRE or AP-1-like site [5].
• A single copy of AR1 inserted upstream of the herpesvirus TK promoter rendered this heterologous promoter inducible by IL-1 alpha, tumor necrosis factor, and serum as well as by activators of the protein kinase A (forskolin) and protein kinase C (phorbol ester) signal transduction pathways [5].

Biological context of TCF20

• Functional mapping revealed that SPBP is a nuclear, multidomain protein containing an N-terminal region with transactivating ability, a novel type of DNA-binding domain containing an AT hook motif, and a bipartite nuclear localization signal as well as a C-terminal zinc finger domain [6].
• The human SPBP gene contains six exons and is located on chromosome 22q13.1-13 [6].
• Assignment of AR1, transcription factor 20 (TCF20), to human chromosome 22q13.3 with somatic cell hybrids and in situ hybridization [7].
• Antibody responses directed against virus-encoded antigens were intact in IFN-AR1(-/-) mice, suggesting that other signals are sufficient to drive immune responses against virally encoded antigens [8].
• Here we show that CR3-mediated transactivation of all adenovirus early promoters and the HSP70 promoter requires the AR1 element [2].

Associations of TCF20 with chemical compounds

• Vitamin E (alpha-tocopherol), other antioxidants and high fat diets can delay or prevent cataract in diabetic animals even though sorbitol and fructose levels are not modified; vitamin C acts as an AR1 in humans [9].
• The cytosolic binding component sediments at 5.6-5.7S in a 5-20% sucrose gradient and is not affected by sodium molybdate, which suggests that AR1 does not interact with heat shock proteins in the usual manner [10].
• In contrast, AR1 is highly specific for only a few androgens, with T = 100% relative binding affinity >> DHT >> 11-ketotestosterone > mibolerone > 17alpha-methyl-5alpha-dihydrotestosterone = 0, has rapid association (t1/2, 15 min) and dissociation (t1/2, 2.6 +/- 0.7 h) rates, and has specific binding to purified DNA upon heat activation [10].
• Calcium-channel blockers, including (-8%, P = 0.07) or excluding verapamil (-10%, P = 0.02), as well as AR1 blockers (-24%, P = 0.0002) resulted in better stroke prevention than did the old drugs, whereas the opposite trend was observed for ACE inhibitors (+10%, P = 0.03) [11].
• In the mature cyst, PHB, AR1, and AR2 account for 8, 5.6, and 4.5%, respectively, of the dry weight [12].

Analytical, diagnostic and therapeutic context of TCF20

• PCR analyses of multitissue cDNA panels showed that SPBP is expressed in most tissues except for ovary and prostate [6].
• Genetic dissection of AR1 showed that the number of EP repeats in AR1 is critical for CR3 function [2].
• In addition, no protein binding to AR1 could be detected by gel mobility shift assay using nuclear extracts from either OK cells or from rat kidney tissue [13].
• The mean +/- S.D. ELISA O.D. obtained for AR1 were 0.73 +/- 0.2, 1.037 +/- 0.196, 1.05 +/- 0.42 and for Pf, 0.70 +/- 0.2, 1.0 +/- 0.28, 0.94 +/- 0.4 respectively for Badramoli, Jharbeda and Boneikela population [14].
• A cross-sectional seroepidemiological study conducted in 173 tribal residents (including all age groups) from three villages of Sundergarh district of Orissa using ELISA as a tool revealed high levels of antibody titres against both AR1 and Pf antigens [14].

References