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HERO ID
1508577
Reference Type
Journal Article
Title
NF-κB1 p50 promotes p53 protein translation through miR-190 downregulation of PHLPP1
Author(s)
Yu, Y; Zhang, D; Huang, H; Li, J; Zhang, M; Wan, Y; Gao, J; Huang, C
Year
2014
Is Peer Reviewed?
1
Journal
Oncogene
ISSN:
0950-9232
EISSN:
1476-5594
Volume
33
Issue
8
Page Numbers
996-1005
Language
English
PMID
23396362
DOI
10.1038/onc.2013.8
Web of Science Id
WOS:000331933200007
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.
Keywords
p50; p53 translation; miR-190; PHLPP1; Akt/S6 ribosomal protein
Tags
IRIS
•
Arsenic Hazard ID
PubMed
Considered New
PubMed
Considered New
ToxNet
Considered New
ToxNet
Excluded
Toxnet Duplicates
ToxNet
Excluded
Toxnet Duplicates
ToxNet
Excluded
Toxnet Duplicates
2. Lit Search Updates through Oct 2015
PubMed
ToxNet
Considered
7. Other Studies through Oct 2015
Non-Arsenic
•
Arsenic (Inorganic)
1. Literature
Lit search updates through Oct 2015
3. Hazard ID Screening
Other potentially supporting studies
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