title: NF-κB1 p50 promotes p53 protein translation through miR-190 downregulation of PHLPP1.
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.
authors: 1] Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA [2] Oversea Laboratory, Center for Medical Research, Wuhan University, Wuhan, Hubei, China.
authors: Y
authors: Y
authors: Yu
authors: Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA.
authors: D
authors: D
authors: Zhang
authors: 1] Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA [2] Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors: H
authors: H
authors: Huang
authors: Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA.
authors: J
authors: J
authors: Li
authors: 1] Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA [2] Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors: M
authors: M
authors: Zhang
authors: Oversea Laboratory, Center for Medical Research, Wuhan University, Wuhan, Hubei, China.
authors: Y
authors: Y
authors: Wan
authors: Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors: J
authors: J
authors: Gao
authors: 1] Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY, USA [2] Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors: C
authors: C
authors: Huang
mesh_terms: D000818:Animals; D018053:Arsenites / Q000494:pharmacology; D001483:Base Sequence; D017931:DNA Primers; D015536:Down-Regulation; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D018053:Arsenites; D017931:DNA Primers; C546705:MIRN190 microRNA, mouse; D035683:MicroRNAs; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D051057:Proto-Oncogene Proteins c-akt; C519282:PHLPP1 protein, mouse; D010749:Phosphoprotein Phosphatases; C015001:arsenite
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