Title: NF-κB1 p50 promotes p53 protein translation through miR-190 downregulation of PHLPP1.
Authors: Yu, Y; Zhang, D; Huang, H; Li, J; Zhang, M; Wan, Y; Gao, J; Huang, C
Published In Oncogene, (2014 Feb 20)
Abstract: The biological function of NF-κB1 (p50) in the regulation of protein expression is far from well understood owing to the lack of a transcriptional domain. Here, we report a novel function of p50 in its regulation of p53 protein translation under stress conditions. We found that the deletion of p50 (p50-/-) impaired arsenite-induced p53 protein expression, which could be restored after reconstitutive expression of HA-p50 in p50-/- cells, p50-/-(Ad-HA-p50). Further studies indicated that the amounts of p53 mRNA, p53 promoter-driven transcription activity and p53 protein degradation were comparable between wild-type and p50-/- cells. Moreover, we found that p50 was crucial for Akt/S6 ribosomal protein activation via inhibition of the translation of the PH domain and leucine-rich repeat protein phosphatases 1 (PHLPP1), a phosphatase of Akt. Further studies showed that p50-mediated upregulation of miR-190 was responsible for the inhibition of PHLPP1 translation by targeting the 3'-untranslated region of its mRNA. Collectively, we have identified a novel function of p50 in modulating p53 protein translation via regulation of the miR-190/PHLPP1/Akt-S6 ribosomal protein pathway.
PubMed ID: 23396362
MeSH Terms: Animals; Arsenites/pharmacology; Base Sequence; DNA Primers; Down-Regulation*; Mice; Mice, Knockout; MicroRNAs/genetics*; NF-kappa B p50 Subunit/genetics; NF-kappa B p50 Subunit/physiology*; Nuclear Proteins/physiology*; Phosphoprotein Phosphatases/physiology*; Protein Biosynthesis/physiology*; Proto-Oncogene Proteins c-akt/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Tumor Suppressor Protein p53/genetics*