http://purl.uniprot.org/citations/18787102 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/18787102 | http://www.w3.org/2000/01/rdf-schema#comment | "Inflammatory bowel disease (IBD) is thought to result from commensal flora, aberrant cellular stress, and genetic factors. Here we show that the expression of colonic Ste20-like proline-/alanine-rich kinase (SPAK) that lacks a PAPA box and an F-alpha helix loop is increased in patients with IBD. The same effects were observed in a mouse model of dextran sodium sulfate-induced colitis and in Caco2-BBE cells treated with the pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha. The 5'-flanking region of the SPAK gene contains two transcriptional start sites, three transcription factor Sp1-binding sites, and one transcription factor nuclear factor (NF)-kappaB-binding site, but no TATA elements. The NF-kappaB-binding site was essential for stimulated SPAK promoter activity by TNF-alpha, whereas the Sp1-binding sites were important for basal promoter activity. siRNA-induced knockdown of NF-kappaB, but not of Sp1, reduced TNF-alpha-induced SPAK expression. Nuclear run-on and mRNA decay assays demonstrated that TNF-alpha directly increased SPAK mRNA transcription without affecting SPAK mRNA stability. Furthermore, up-regulation of NF-kappaB expression and demethylation of the CpG islands induced by TNF-alpha also played roles in the up-regulation of SPAK expression. In conclusion, our data indicate that during inflammatory conditions, TNF-alpha is a key regulator of SPAK expression. The development of compounds that can either modulate or disrupt the activity of SPAK-mediated pathways is therefore important for the control and attenuation of downstream pathological responses, particularly in IBD."xsd:string |
http://purl.uniprot.org/citations/18787102 | http://purl.org/dc/terms/identifier | "doi:10.2353/ajpath.2008.080339"xsd:string |
http://purl.uniprot.org/citations/18787102 | http://purl.uniprot.org/core/author | "Nguyen H.T."xsd:string |
http://purl.uniprot.org/citations/18787102 | http://purl.uniprot.org/core/author | "Yan Y."xsd:string |
http://purl.uniprot.org/citations/18787102 | http://purl.uniprot.org/core/author | "Dalmasso G."xsd:string |
http://purl.uniprot.org/citations/18787102 | http://purl.uniprot.org/core/author | "Merlin D."xsd:string |
http://purl.uniprot.org/citations/18787102 | http://purl.uniprot.org/core/author | "Obertone T.S."xsd:string |
http://purl.uniprot.org/citations/18787102 | http://purl.uniprot.org/core/author | "Sitaraman S.V."xsd:string |
http://purl.uniprot.org/citations/18787102 | http://purl.uniprot.org/core/author | "Charrier-Hisamuddin L."xsd:string |
http://purl.uniprot.org/citations/18787102 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
http://purl.uniprot.org/citations/18787102 | http://purl.uniprot.org/core/name | "Am J Pathol"xsd:string |
http://purl.uniprot.org/citations/18787102 | http://purl.uniprot.org/core/pages | "1013-1028"xsd:string |
http://purl.uniprot.org/citations/18787102 | http://purl.uniprot.org/core/title | "Nuclear factor-kappaB is a critical mediator of Ste20-like proline-/alanine-rich kinase regulation in intestinal inflammation."xsd:string |
http://purl.uniprot.org/citations/18787102 | http://purl.uniprot.org/core/volume | "173"xsd:string |
http://purl.uniprot.org/citations/18787102 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18787102 |
http://purl.uniprot.org/citations/18787102 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18787102 |
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