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PATZ1 induces PP4R2 to form a negative feedback loop on IKK/NF-κB signaling in lung cancer.

Oncotarget. 2016-10; 
HoMing-Yi,LiangChi-Ming,LiangShu
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Custom Vector Construction … To examine transcriptional regulation of PP4R2 gene promoter, approximately 3 kb of the PP4R2 promoter (−2500/+500) was synthesized by GenScript (Genscript Corporation, Piscataway, NJ) and subcloned into the pGL3-basic vector (Promega, Madison, WI) to generate the … Get A Quote

摘要

Activation of IKK enhances NF-κB signaling to facilitate cancer cell migration, invasion and metastasis. Here, we uncover the existence of a negative feedback loop of IKK. The transcription factor PATZ1 induces protein phosphatase-4 (PP4) regulatory subunit 2 (PP4R2) in an IKK-dependent manner. PP4R2 enhances the binding of PP4 to phosphorylated IKK to inactivate IKK/NF-κB signaling during sustained stimulation by cellular stimuli such as growth factors and inflammatory mediators. Matched pair studies reveal that primary lung cancers express more PATZ1 and PP4R2 than lymph node metastases in patients. Ectopic PATZ1 decreases invasion/colonization of lung cancers and prolongs the survival of xenograft mice... More

关键词

IκB kinase (IKK),PATZ1,epithelial-mesenchymal transition (EMT),migration/invasion/metastasis,protein phosphatase 4 (