Disease relevance of Sp1

• The three approaches consistently yielded reduced levels of Sp1 which ameliorated toxicity caused by either mutant Htt or 3-NP [1].
• When these same constructs were transfected into MCF-7 human breast cancer cells or were cotransfected with an Sp1 expression vector in Drosophila SL2 cells, similar results were obtained [2].
• BTEB and Sp1 activated the expression of genes with repeated GC box sequences in promoters such as the simian virus 40 early promoter and the human immunodeficiency virus-1 long terminal repeat promoter [3].
• Role of O-linked beta-N-acetylglucosamine modification in the subcellular distribution of alpha4 phosphoprotein and Sp1 in rat lymphoma cells [4].
• Here we report the temporal dynamics of accumulation of total, O-GlcNAc-modified, and phosphorylated Sp1 in H-411E hepatoma cells by immunohistochemistry with monospecific antibodies, confocal microscopy, and matrix-assisted laser desorption and ionization-time of flight mass spectrometry [5].

Psychiatry related information on Sp1

• Sp1 is up-regulated in cellular and transgenic models of Huntington disease, and its reduction is neuroprotective [1].

High impact information on Sp1

• Sp1, whose binding site in the PDGF-B promoter overlaps that of Egr-1, occupies this element in unstimulated cells and is displaced by increasing amounts of Egr-1 [6].
• Here, we investigate the mechanisms of Sp1 pre-mRNA trans-splicing with human cells expressing modified Sp1 transgenes [7].
• These results suggest that high blood pressure is a stimulus which upregulates PDGF A-chain gene expression in VSMCs of SHRs, resulting in an autocrine enhancement in hypertensive vascular hypertrophy, and that the activation of the gene may be mediated through increases in Sp1 in these cells [8].
• While one is for the rat equivalent to human Sp1, the other encodes a primary structure of 244 amino acids, a novel DNA binding protein designated BTEB [3].
• This enhancer can activate comparably well promoters containing binding sites for either glucocorticoid receptor, Sp1 factor, or octamer factor [9].

Chemical compound and disease context of Sp1

• Insulin deprivation leads to deficiency of Sp1 transcription factor in H-411E hepatoma cells and in streptozotocin-induced diabetic ketoacidosis in the rat [10].

Biological context of Sp1

• Force application increased association of Sp1 with p38 and phosphorylation of Sp1 [11].
• Sp1 inhibits proliferation and induces apoptosis in vascular smooth muscle cells by repressing p21WAF1/Cip1 transcription and cyclin D1-Cdk4-p21WAF1/Cip1 complex formation [12].
• Sp1 levels were also elevated when 3-nitropropionate (3-NP) was used to induce cell death in PC12 cells [1].
• Chromatin immunoprecipitation analysis, using rat hepatocytes, demonstrated that SREBP-1 and Sp1 were associated in vivo with putative regulatory regions corresponding to the SREs in the PEPCK-C gene promoter [13].
• Sequence analysis detected five putative Sp1 binding sites in the -127/+37-bp sequence [14].

Anatomical context of Sp1

• A highly active homeobox gene promoter regulated by Ets and Sp1 family members in normal granulosa cells and diverse tumor cell types [15].
• Coexpression studies using an IGF-I-R promoter reporter construct together with an Sp1 expression vector (under the control of an ADH promoter) were performed in SL2 cells, a Drosophila cell line which lacks endogenous Sp1 [16].
• A 95- to 105-kDa form of Sp1 is most abundant in the tissues and cell lines examined, but a 60-kDa form of Sp1 is the most abundant species in spermatocytes and early spermatids [17].
• In contrast, only elements C, D, and E are bound by Sp1 in endothelial cells [18].
• These findings suggest that Sp1 is involved in the regulation of rGLUT1 gene expression during rat trophoblast differentiation [19].

Associations of Sp1 with chemical compounds

• Carvedilol effectively blocks oxidative stress-mediated downregulation of sarcoplasmic reticulum Ca2+-ATPase 2 gene transcription through modification of Sp1 binding [20].
• Involvement of nuclear transcription factor Sp1 in regulating glucose transporter-1 gene expression during rat trophoblast differentiation [19].
• Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via an Sp1-dependent pathway [21].
• Insulin stimulates and diabetes inhibits O-linked N-acetylglucosamine transferase and O-glycosylation of Sp1 [22].
• Cholesterol biosynthesis from lanosterol. A concerted role for Sp1 and NF-Y-binding sites for sterol-mediated regulation of rat 7-dehydrocholesterol reductase gene expression [23].
• By oligonucleotide precipitation assay, IL-6 rapidly promoted a complex containing both Sp1/3 and Stat1/3 on the Sp1/3 elements [24].

Physical interactions of Sp1

• Sp1 and Sp3 transcription factors were subsequently identified to bind to oligonucleotide probes corresponding to only the two most proximal Sp1 sites [25].
• The analysis showed that the Sp1 binding site is a likely target of IGF-1 action [26].
• In nuclear extracts from control PC12 cells, an oligonucleotide containing the TH Sp1/Egr1 motif binds Sp1-containing complexes [27].
• Supershift mobility assays, site-directed mutagenesis and DNase I footprints indicated that Sp1 binds to three GC boxes within the sequence between -128 and -14 of the PLC-beta 3 promoter [28].
• Six Sp1 binding sites and CAAT box exist in the region from transcription start site to -419 bp which showed the highest promoter activity in ACL promoter previously [29].

Enzymatic interactions of Sp1

• Thus, expression of the PNMT gene seems to be modulated through competitive binding of phosphorylated Sp1 and MAZ to their consensus elements in the promoter [30].

Regulatory relationships of Sp1

• Sp1 down-regulated p21WAF1/Cip1 expression in SMCs [12].
• We found increased levels of Sp1 in neuronal-like PC12 cells expressing mutant Htt, primary striatal neurons, and brain tissue of HD transgenic mice [1].
• SREBP-1c and Sp1 interact to regulate transcription of the gene for phosphoenolpyruvate carboxykinase (GTP) in the liver [13].
• In conclusion, hepatocyte PAI-1 expression is flow sensitive and transcriptionally regulated by shear stress via cooperative interactions between Sp1 and Ets-1 [31].
• Transcription factor Sp1 phosphorylation induced by shear stress inhibits membrane type 1-matrix metalloproteinase expression in endothelium [32].

Other interactions of Sp1

• SMC proliferation inducible by a dominant-negative mutant form of Sp1 was abrogated by antisense strategies targeting p21WAF1/Cip1 [12].
• In the current study, we characterized the relationship of Sp1 to Htt protein aggregation and neuronal cell death [1].
• IGF-I treatment also increased Sp1 protein levels and binding activity [14].
• Insulin-like growth factor I increases rat peptide YY promoter activity through Sp1 binding sites [14].
• 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 [17].

Analytical, diagnostic and therapeutic context of Sp1

• Electrophoretic mobility shift assays showed that transcription factors Sp1 and Sp3 bound two GC boxes in the region -99/-33 bp of the rGLUT1 promoter [19].
• Site-directed mutagenesis revealed that two Sp1 sites in the SERCA2 gene promoter region mediated the response to carvedilol under oxidative stress [20].
• Using DNA microarray to identify Sp1 as a transcriptional regulatory element of insulin-like growth factor 1 in cardiac muscle cells [26].
• CONCLUSIONS: The Sp1-Stat3 complex appears to play an important role in the upregulation of ICAM-1 transcription after reoxygenation or reperfusion [33].
• We also examined the phosphorylation of Sp1 using both Western blot and incorporation of 32P into Sp1 [22].

References