Disease relevance of SP1

• Expression of the hypoxia marker carbonic anhydrase IX is critically dependent on SP1 activity. Identification of a novel type of hypoxia-responsive enhancer [1].
• Of these, three were completely competed with the SP1 and transforming growth factor-beta retinoblastoma control-element CACCC box (RCE) probes, whereas the AP2 probe competed against the same three complexes partially [2].
• Accordingly, H/R-stimulated melanoma cells showed enhanced binding activity of both transcription factors NF-kappaB and SP1 in electrophoretic mobility-shift assay [3].
• Conserved POU-binding site linked to SP1-binding site within FZD5 promoter: Transcriptional mechanisms of FZD5 in undifferentiated human ES cells, fetal liver/spleen, adult colon, pancreatic islet, and diffuse-type gastric cancer [4].
• Celecoxib inhibits vascular endothelial growth factor expression in and reduces angiogenesis and metastasis of human pancreatic cancer via suppression of Sp1 transcription factor activity [5].

Psychiatry related information on SP1

• Sp1 transcription factor expression was examined by immunohistochemistry, immunofluorescence and confocal microscopy in Alzheimer disease (AD), Pick disease (PiD), progressive supranuclear palsy (PSP), Parkinson disease (PD) and Dementia with Lewy bodies (DLB) [6].

High impact information on SP1

• Synergistic activation by the glutamine-rich domains of human transcription factor Sp1 [7].
• Here we show that the human RNA polymerase II transcription factor Sp1 bears multiple O-linked N-acetylglucosamine (GlcNAc) monosaccharide residues [8].
• The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter [9].
• In two unrelated kindreds, a point mutation (c --> g) at position -270 from the start codon of PIGM, a mannosyltransferase-encoding gene, disrupts binding of the transcription factor Sp1 to its cognate promoter motif [10].
• In addition, non-tissue-specific protein-promoter interactions involving the Sp1 transcription factor are necessary for hPL transcription initiation [11].

Chemical compound and disease context of SP1

• It has been proposed that intense immunohistochemical staining using the monoclonal antibody NCRC 11 is indicative of a better prognosis in breast cancer, and that expression of pregnancy specific glycoprotein (SP1) and epidermal growth factor receptors (EGFR) are poor prognosis indicators [12].
• The authors developed the first rabbit antiestrogen receptor monoclonal antibody (clone SP1) used in immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections especially from breast carcinomas [13].
• Since hyperglycemia-induced mitochondrial superoxide overproduction increases O-linked N-acetylglucosamine modification and decreases O-linked phosphorylation of the transcription factor Sp1, the effect of hyperglycemia and the hexosamine pathway on eNOS was evaluated [14].
• SPase is a cysteine protease isolated from an African green monkey kidney cell line, CV-1, and has selective cleavage activity toward transcription factor SP-1 and retinoblastoma susceptibility gene product RB [15].
• Cellular localization of AFP, hCG and its free subunits, and SP1 in embryonal carcinoma of the testis and ovary [16].

Biological context of SP1

• Using site directed mutagenesis, we show that the -37 GATA and the -50 SP1 binding sites are necessary for efficient activity of the -95 GPB construct [17].
• This transactivation is abolished by mutations that impair either the -37 GATA-1 or the -50 SP1 binding [17].
• The -69/+20 promoter region contains an overlapping SP1/EGR site [18].
• The murine HDAC1 promoter lacks a TATA box consensus sequence but contains several putative SP1 binding sites and a CCAAT box, which is recognized by the transcription factor NF-Y [19].
• As shown by electromobility shift assays and block-replacement mutagenesis, PR5 is functionally equivalent to the SP1/SP3-binding PR1 identified previously [1].

Anatomical context of SP1

• CONCLUSION/INTERPRETATION: SP1 is expressed and its binding activity is enhanced during adipocyte differentiation [20].
• Activation of AP-1 and SP1 correlates with wound growth factor gene expression in glucan-treated human fibroblasts [21].
• Regulation of leukotriene C4 synthase gene expression by SP1 and SP3 in mononuclear phagocytes [22].
• Among eight human glioma cell lines, cellular mRNA levels of transcription factors SP-1 and AP-1 (c-Fos and c-Jun) were found to be closely correlated with those of VEGF [23].
• Our data suggest that intracellular, but not extracellular, transition metal ions mediate inflammatory cytokine-induced SP-1 activation and adhesion molecule expression in endothelial cells [24].

Associations of SP1 with chemical compounds

• Increased histone acetylation at the HDAC1 promoter region in response to TSA treatment is dependent on binding sites for SP1 and NF-Y [19].
• Inhibitors of PI3-kinase or SP-1 blocked both progesterone- and MPA-induced increases in VEGF mRNA levels in T47-DCO cells [25].
• The proximal SP-1 sites within the VEGF promoter were critical for progestin-dependent induction of VEGF [25].
• The Sp1 transcription factor contributes to the tumor necrosis factor-induced expression of the angiogenic factor thymidine phosphorylase in human colon carcinoma cells [26].
• Androgen induction of cyclin-dependent kinase inhibitor p21 gene: role of androgen receptor and transcription factor Sp1 complex [27].

Physical interactions of SP1

• The proximal region, -1 to -60, contains a GATA binding sequence around -37 and an SP1 binding sequence around -50 [17].
• This VHL-responsive element is GC rich and specifically binds the transcription factor Sp1 in crude nuclear extracts [28].
• Three of the four MAZ binding sites also were shown to interact with transcription factor Sp1 [29].
• The p21 core promoter is GC-rich and contains six binding sites for transcription factor Sp1 [27].
• BACKGROUND: Estrogens can upregulate endothelial nitric oxide synthase (eNOS) in human endothelial cells by increasing eNOS promoter activity and enhancing the binding activity of the transcription factor Sp1 [30].

Regulatory relationships of SP1

• The role of the transcription factor Sp1 in regulating the expression of the WAF1/CIP1 gene in U937 leukemic cells [31].
• Among known transcription factors that have binding sites in the promoter region of the VCAM-1 gene, IL-4 activated only SP-1 [32].
• In this study, we show that the transcription factor Sp1 binds and activates the utrophin promoter in Drosophila S2 cells as well as define a Sp1 response element [33].
• The human caspase-8 promoter sustains basal activity through SP1 and ETS-like transcription factors and can be up-regulated by a p53-dependent mechanism [34].
• These results provide the first demonstration that CTR can induce gene transcription through the constitutively expressed transcription factor Sp1, and define a mechanism of cell growth suppression that may have implications for other members of the seven-transmembrane domain G protein-coupled receptor superfamily [35].

Other interactions of SP1

• Finally, the expression of EGR1 was sufficient to activate a construct containing tandem MDR1 promoter SP1/EGR sites [18].
• Constitutive activation of the transcription factor Sp1 plays a critical role in VEGF overexpression [5].
• The transcription factor Sp1 may be involved in the repression of VEGF promoter activity by wt p53 in SKLMS-1 cells [36].
• The human reduced folate carrier gene is regulated by the AP2 and sp1 transcription factor families and a functional 61-base pair polymorphism [37].
• Role of Smad proteins and transcription factor Sp1 in p21(Waf1/Cip1) regulation by transforming growth factor-beta [38].

Analytical, diagnostic and therapeutic context of SP1

• Chromatin immunoprecipitation assays showed that HDAC1 is recruited to the promoter by SP1 and NF-Y, thereby regulating its own expression [19].
• By sequence analysis putative regulatory elements in the promoter domain were shown to include a TATA box and several conserved binding sites for stimulatory protein 1 (SP1) and activator protein 2 (AP2) [39].
• Molecular dissection of the MTA3 promoter using transient transfection assays identified a composite element required for high-level transcription consisting of an SP1 site in close proximity to a consensus estrogen response element half-site [40].
• Southern blot analysis of genomic DNA from a panel of mouse x human somatic cell hybrids indicated that SP1 was localized to chromosome 12 [41].
• In situ hybridization allowed the localization of the gene encoding SP1 to human chromosome 12q12-->q13.2, with 12q13.1 being the most probable location [41].

References