| http://purl.uniprot.org/citations/14623898 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/14623898 | http://www.w3.org/2000/01/rdf-schema#comment | "The PTEN (phosphatase and tensin homolog deleted on chromosome ten) tumor suppressor gene affects multiple cellular processes including cell growth, proliferation, and cell migration by antagonizing phosphatidylinositol 3-kinase (PI3K). However, mechanisms by which PTEN expression is regulated have not been studied extensively. Similar to PTEN, tumor necrosis factor-alpha (TNF-alpha) affects a wide spectrum of diseases including inflammatory processes and cancer by acting as a mediator of apoptosis, inflammation, and immunity. In this study, we show that treatment of cancer cell lines with TNF-alpha decreases PTEN expression. In addition, overexpression of TNF-alpha downstream signaling targets, nuclear factor-kappaB (NF-kappaB)-inducing kinase (NIK) and p65 nuclear factor NF-kappaB, lowers PTEN expression, suggesting that TNF-alpha-induced down-regulation of PTEN is mediated through a TNF-alpha/NIK/NF-kappaB pathway. Down-regulation of PTEN by NIK/NF-kappaB results in activation of the PI3K/Akt pathway and augmentation of TNF-alpha-induced PI3K/Akt stimulation. Importantly, we demonstrate that this effect is associated with a lack of an inhibitor of kappaB (IkappaB)-alpha autoregulatory loop. Moreover, these findings suggest the interaction between PI3K/Akt and NF-kappaB via transcriptional regulation of PTEN and offer one possible explanation for increased tumorigenesis in systems in which NF-kappaB is chronically activated. In such a tumor system, these findings suggest a positive feedback loop whereby Akt activation of NF-kappaB further stimulates Akt via down-regulation of the PI3K inhibitor PTEN."xsd:string |
| http://purl.uniprot.org/citations/14623898 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m308383200"xsd:string |
| http://purl.uniprot.org/citations/14623898 | http://purl.uniprot.org/core/author | "Kang J."xsd:string |
| http://purl.uniprot.org/citations/14623898 | http://purl.uniprot.org/core/author | "Kim S."xsd:string |
| http://purl.uniprot.org/citations/14623898 | http://purl.uniprot.org/core/author | "Chung D.H."xsd:string |
| http://purl.uniprot.org/citations/14623898 | http://purl.uniprot.org/core/author | "Domon-Dell C."xsd:string |
| http://purl.uniprot.org/citations/14623898 | http://purl.uniprot.org/core/author | "Freund J.N."xsd:string |
| http://purl.uniprot.org/citations/14623898 | http://purl.uniprot.org/core/author | "Evers B.M."xsd:string |
| http://purl.uniprot.org/citations/14623898 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/14623898 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/14623898 | http://purl.uniprot.org/core/pages | "4285-4291"xsd:string |
| http://purl.uniprot.org/citations/14623898 | http://purl.uniprot.org/core/title | "Down-regulation of the tumor suppressor PTEN by the tumor necrosis factor-alpha/nuclear factor-kappaB (NF-kappaB)-inducing kinase/NF-kappaB pathway is linked to a default IkappaB-alpha autoregulatory loop."xsd:string |
| http://purl.uniprot.org/citations/14623898 | http://purl.uniprot.org/core/volume | "279"xsd:string |
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