ConTra v2: a tool to identify transcription factor binding sites across species, update 2011

Broos, Stefan; Hulpiau, Paco; Galle, Jeroen; Hooghe, Bart; Roy, Frans Van; Bleser, Pieter De

doi:10.1093/nar/gkr355

Cited by 55 publications

(46 citation statements)

References 21 publications

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“…Putative transcription factor-binding sites in the VEGFA promoter and intron 1 region were identified using the web-based analysis tool ConTra (Broos et al, 46 ). In a Multiz alignment of the promoter (2000 upstream) and first intronic region of VEGFA from different species, highly conserved binding sites were detected for p53, HIF1-a.…”

Section: Methodsmentioning

confidence: 99%

p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway

et al. 2013

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There is growing evidence that the p53 tumour suppressor downregulates vascular endothelial growth factor (VEGF) expression, although the underlying mechanisms remain unclear and controversial. Here we provide insights from in vitro experiments and in vivo xenotransplantation assays that highlight a dual role for p53 in regulating VEGF during hypoxia. Unexpectedly, and for the first time, we demonstrate that p53 rapidly induces VEGF transcription upon hypoxia exposure by binding, in an HIF-1a-dependent manner, to a highly conserved and functional p53-binding site within the VEGF promoter. However, during sustained hypoxia, p53 indirectly downregulates VEGF expression via the retinoblastoma (Rb) pathway in a p21-dependent manner, which is distinct from its role in cell-cycle regulation. Our findings have important implications for cancer therapy, especially for tumours that harbour wild-type TP53 and a dysfunctional Rb pathway.

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Section: Methodsmentioning

confidence: 99%

p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway

et al. 2013

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“…4B, middle and right), the mRNA expression of IGF2 in ESCC cell lines, indicating that E2F1 regulates IGF2 expression at both protein and mRNA levels. Next, two software programs that predict transcription factor-binding sites, namely ConTra V2 and TRRD (25,26), were used to search for potential E2F1-binding sites (BS) in the IGF2 promoter region, and three potential binding sites (designated BS1, BS2, and BS3) were identified by both software, which suggested that E2F1 may bind directly to the IGF2 promoter and activate IGF2 transcription (Fig. 4C).…”

Section: E2f1 Mediates Id1-induced Upregulation Of Igf2 By Binding DImentioning

confidence: 99%

Competitive Binding Between Id1 and E2F1 to Cdc20 Regulates E2F1 Degradation and Thymidylate Synthase Expression to Promote Esophageal Cancer Chemoresistance

Guan

et al. 2016

Clinical Cancer Research

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Purpose: Chemoresistance is a major obstacle in cancer therapy. We found that fluorouracil (5-FU)-resistant esophageal squamous cell carcinoma cell lines, established through exposure to increasing concentrations of 5-FU, showed upregulation of Id1, IGF2, and E2F1. We hypothesized that these genes may play an important role in cancer chemoresistance.Experimental Design: In vitro and in vivo functional assays were performed to study the effects of Id1-E2F1-IGF2 signaling in chemoresistance. Quantitative real-time PCR, Western blotting, immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays were used to investigate the molecular mechanisms by which Id1 regulates E2F1 and by which E2F1 regulates IGF2. Clinical specimens, tumor tissue microarray, and Gene Expression Omnibus datasets were used to analyze the correlations between gene expressions and the relationships between expression profiles and patient survival outcomes.Results: Id1 conferred 5-FU chemoresistance through E2F1-dependent induction of thymidylate synthase expression in esophageal cancer cells and tumor xenografts. Mechanistically, Id1 protects E2F1 protein from degradation and increases its expression by binding competitively to Cdc20, whereas E2F1 mediates Id1-induced upregulation of IGF2 by binding directly to the IGF2 promoter and activating its transcription. The expression level of E2F1 was positively correlated with that of Id1 and IGF2 in human cancers. More importantly, concurrent high expression of Id1 and IGF2 was associated with unfavorable patient survival in multiple cancer types.Conclusions: Our findings define an intricate E2F1-dependent mechanism by which Id1 increases thymidylate synthase and IGF2 expressions to promote cancer chemoresistance. The Id1-E2F1-IGF2 regulatory axis has important implications for cancer prognosis and treatment. Clin Cancer Res; 22(5); 1243-55. Ó2015 AACR.

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“…Subsequently the ConTra v2 software (Broos et al 2011) was applied to identify potential heat shock factor (HSF) binding sites. Default software parameters were used for the analyses.…”

Section: Analysis Of Cis-regulatory Sequences Of Crmp1mentioning

confidence: 99%

Systematic interaction network filtering identifies CRMP1 as a novel suppressor of huntingtin misfolding and neurotoxicity

et al. 2015

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Assemblies of huntingtin (HTT) fragments with expanded polyglutamine (polyQ) tracts are a pathological hallmark of Huntington's disease (HD). The molecular mechanisms by which these structures are formed and cause neuronal dysfunction and toxicity are poorly understood. Here, we utilized available gene expression data sets of selected brain regions of HD patients and controls for systematic interaction network filtering in order to predict disease-relevant, brain region-specific HTT interaction partners. Starting from a large protein-protein interaction (PPI) data set, a step-by-step computational filtering strategy facilitated the generation of a focused PPI network that directly or indirectly connects 13 proteins potentially dysregulated in HD with the disease protein HTT. This network enabled the discovery of the neuron-specific protein CRMP1 that targets aggregation-prone, N-terminal HTT fragments and suppresses their spontaneous self-assembly into proteotoxic structures in various models of HD. Experimental validation indicates that our network filtering procedure provides a simple but powerful strategy to identify disease-relevant proteins that influence misfolding and aggregation of polyQ disease proteins.

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ConTra v2: a tool to identify transcription factor binding sites across species, update 2011

Cited by 55 publications

References 21 publications

p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway

p53 promotes VEGF expression and angiogenesis in the absence of an intact p21-Rb pathway

Competitive Binding Between Id1 and E2F1 to Cdc20 Regulates E2F1 Degradation and Thymidylate Synthase Expression to Promote Esophageal Cancer Chemoresistance

Systematic interaction network filtering identifies CRMP1 as a novel suppressor of huntingtin misfolding and neurotoxicity

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