Disease relevance of Sp3

• To test whether other members of the Sp family are direct targets of insulin action, we compared the levels of Sp1 and Sp3 proteins from nuclear extracts obtained from both insulin-treated and untreated rat hepatoma (H-411E) cells [1].

High impact information on Sp3

• Increased expression of p27(Kip1) increases the level of Sp1 promoter binding to the GC box but does not change the level of Sp3 binding [2].
• The results have demonstrated that Kir6.2 promoter possesses two regions regulating the promoter activity: a Foxa2-binding site (-1364 to -1210) and an Sp1/Sp3-binding site (-1035 to -939) [3].
• Thus, regulation of Sp1/Sp3 recruitment to the promoter may represent a potential general mechanism for transcriptional control of target genes by signals passing through gap junctions [4].
• Tyrosine phosphorylation of one Sp3 form was decreased, whereas phosphorylation of two other forms of Sp3 was increased in nuclear extracts of Ha-Ras-transformed cells [5].
• Expression of several forms of Sp3 was increased in nuclear extracts of Ha-Ras-transformed fibroblasts compared with nontransformed cells [5].

Biological context of Sp3

• Modulation of Sp1/Sp3 recruitment also occurs on the collagen Ialpha1 promoter and translates into gap junction-sensitive transcriptional control of collagen Ialpha1 gene expression [4].
• Lastly, chromatin immunoprecipitation analyses revealed that both Sp1 and Sp3 bind to the GIPR promoter region in RIN38 cells [6].
• The Sp1/Sp3-binding motif within rat LINE1 promoter is located downstream of the major predicted transcription initiation site [7].
• We correlate the protective effects of mithramycin A with its ability to inhibit enhanced DNA binding of the transcription factors Sp1 and Sp3 to their cognate "G-C" box induced by oxidative stress or DNA damage [8].
• The transactivation is dependent upon an intact E2 and may involve direct interactions between Sp1 and Sp3 [9].

Anatomical context of Sp3

• Gap junctional communication modulates gene transcription by altering the recruitment of Sp1 and Sp3 to connexin-response elements in osteoblast promoters [4].
• Because GC-box is a consensus site for binding of Sp transcription-factor family members, experiments were performed demonstrating that two Sp family members, Sp1 and Sp3, were present in testis cells from 9-day-old and adult rats and in pachytene primary spermatocytes and early spermatids [10].
• This study was carried out to investigate the immunolocalization of Sp3 during the development of rat tooth germs [11].
• Immunohistochemical localization of transcription factor Sp3 during dental enamel development in rat tooth germ [11].
• Sp3 was found to be localized within the nuclei of cells in developing tooth germs; however, ameloblast nuclei showed variable intensities at different developmental stages [11].

Associations of Sp3 with chemical compounds

• Sp1 and Sp3 regulate expression of the neuronal nicotinic acetylcholine receptor beta4 subunit gene [9].
• GLUT1 glucose transporter gene transcription is repressed by Sp3. Evidence for a regulatory role of Sp3 during myogenesis [12].
• Further, electrophoretic mobility shift assays revealed that Sp1 and Sp3 transcription factors correlated with carvedilol-mediated changes in the promoter assays [13].
• Perinatal regulation of the ClC-2 chloride channel in lung is mediated by Sp1 and Sp3 [14].
• Finally, malondialdehyde increased cellular levels of the Sp1 and Sp3 proteins and Sp1 mRNA [15].

Physical interactions of Sp3

• We identified an Sp1/Sp3 containing complex that assembles on a minimal element in the -70 to -57 region of the osteocalcin promoter in a gap junction-dependent manner [4].
• Sp1 and Sp3 binding also occurred downstream from or overlapping the Egr-1 binding site in the rat alpha7 promoter [16].
• Sp1 has been identified as one of the factors whose binding is lost, and in the present study we show that Sp3 binding is also abrogated by IGF-I, but in a selected manner [17].
• Moreover, Sp1 and Sp3 proteins interacted with the proximal and the distal Sp1 sites in the nuclear extracts of gp600/megalin expressing cell lines [18].

Other interactions of Sp3

• These studies indicate that Sp1 and Sp3 may be involved in the regulation of the rat Mrp3 gene [19].
• We demonstrated previously that PDGF-A expression is under the positive regulatory influence of Sp1, Sp3, and Egr-1 and is negatively controlled by GCF2, NF-1(X), and WT-1 [20].
• Overexpression of Sp1 or Sp4, but not Sp3, significantly increased the activity of the promoter containing these elements [21].
• Differential effects of heterogeneous nuclear ribonucleoprotein K on Sp1- and Sp3-mediated transcriptional activation of a neuronal nicotinic acetylcholine receptor promoter [22].
• Competitive gel shift and supershift assays indicated that Sp2 and Sp3 were bound to an Sp1 site (-40/-31), and activating transcription factor-2 and c-Jun were bound to a CRE site [23].

Analytical, diagnostic and therapeutic context of Sp3

• Electrophoretic mobility shift assays (EMSAs) and supershift EMSAs using nuclear extract from INS-1 cells demonstrated that Sp1 and Sp3 bind a GC box while the nuclear factor Y was shown to bind the proximal but not the distal CCAAT box [24].
• Using an EMSA and Southwestern blotting methods, we identified Sp1 and Sp3 proteins, which specifically bind to the rat LINE1 promoter in vitro [7].
• We used electrophoretic mobility shift assays and Western blot analysis to demonstrate that levels of Sp1 and Sp3, two zinc finger transcription factors which mediate basal expression of the PDGF-B gene, are elevated in pup nuclei compared with adult nuclei [25].
• Further site-directed mutagenesis analysis and gel mobility shift assays provided evidence for Sp1 and Sp3 binding within -123/-105 regions [19].
• Immunoblotting techniques demonstrate that Sp1 and Sp3 are perinatally downregulated in the lung with the same temporal sequence as ClC-2 downregulation [14].

References