UXT, a novel MDMX-binding protein, promotes glycolysis by mitigating p53-mediated restriction of NF-κB activity
The importance of stress-induced p53 activation has been extensively investigated and well established. How the basal activity of p53 prevents carcinogenesis, however, remains incompletely understood. We report the identification of a novel p53 inhibitor, UXT, which binds to MDMX and suppresses the...
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| Format: | Online |
| Language: | English |
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Impact Journals LLC
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627330/ |
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pubmed-46273302015-12-02 UXT, a novel MDMX-binding protein, promotes glycolysis by mitigating p53-mediated restriction of NF-κB activity Qi, Min Ganapathy, Suthakar Zeng, Weiqi Zhang, Jianglin Little, John B. Yuan, Zhi-Min Research Paper The importance of stress-induced p53 activation has been extensively investigated and well established. How the basal activity of p53 prevents carcinogenesis, however, remains incompletely understood. We report the identification of a novel p53 inhibitor, UXT, which binds to MDMX and suppresses the basal activity of p53. Interestingly, human TCGA database indicates that the UXT gene is frequently amplified in human sarcoma where p53 mutation is rare. We thus used sarcoma as a model to show that UXT acts as an oncogene promoting cell proliferation in vitro and tumor progression in vivo. A screening of 10 major cellular pathways uncovered that UXT-mediated p53 inhibition results in an activation of NF-κB, leading to induction of glycolysis. While elevated glycolytic metabolism provides growth advantage it also renders UXT expressing sarcoma cells heightened sensitivity to glycolysis inhibition. Altogether, our data demonstrate a crucial role for the basal activity of p53 in restriction of NF-κB. By impeding such an activity of p53, UXT unleashes the oncogenic activity of NF-κB resulting in induction of glycolysis fueling carcinogenesis. Impact Journals LLC 2015-05-07 /pmc/articles/PMC4627330/ /pubmed/25974965 Text en Copyright: © 2015 Qi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Qi, Min Ganapathy, Suthakar Zeng, Weiqi Zhang, Jianglin Little, John B. Yuan, Zhi-Min |
| spellingShingle |
Qi, Min Ganapathy, Suthakar Zeng, Weiqi Zhang, Jianglin Little, John B. Yuan, Zhi-Min UXT, a novel MDMX-binding protein, promotes glycolysis by mitigating p53-mediated restriction of NF-κB activity |
| author_facet |
Qi, Min Ganapathy, Suthakar Zeng, Weiqi Zhang, Jianglin Little, John B. Yuan, Zhi-Min |
| author_sort |
Qi, Min |
| title |
UXT, a novel MDMX-binding protein, promotes glycolysis by mitigating p53-mediated restriction of NF-κB activity |
| title_short |
UXT, a novel MDMX-binding protein, promotes glycolysis by mitigating p53-mediated restriction of NF-κB activity |
| title_full |
UXT, a novel MDMX-binding protein, promotes glycolysis by mitigating p53-mediated restriction of NF-κB activity |
| title_fullStr |
UXT, a novel MDMX-binding protein, promotes glycolysis by mitigating p53-mediated restriction of NF-κB activity |
| title_full_unstemmed |
UXT, a novel MDMX-binding protein, promotes glycolysis by mitigating p53-mediated restriction of NF-κB activity |
| title_sort |
uxt, a novel mdmx-binding protein, promotes glycolysis by mitigating p53-mediated restriction of nf-κb activity |
| description |
The importance of stress-induced p53 activation has been extensively investigated and well established. How the basal activity of p53 prevents carcinogenesis, however, remains incompletely understood. We report the identification of a novel p53 inhibitor, UXT, which binds to MDMX and suppresses the basal activity of p53. Interestingly, human TCGA database indicates that the UXT gene is frequently amplified in human sarcoma where p53 mutation is rare. We thus used sarcoma as a model to show that UXT acts as an oncogene promoting cell proliferation in vitro and tumor progression in vivo. A screening of 10 major cellular pathways uncovered that UXT-mediated p53 inhibition results in an activation of NF-κB, leading to induction of glycolysis. While elevated glycolytic metabolism provides growth advantage it also renders UXT expressing sarcoma cells heightened sensitivity to glycolysis inhibition. Altogether, our data demonstrate a crucial role for the basal activity of p53 in restriction of NF-κB. By impeding such an activity of p53, UXT unleashes the oncogenic activity of NF-κB resulting in induction of glycolysis fueling carcinogenesis. |
| publisher |
Impact Journals LLC |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627330/ |
| _version_ |
1613495346084708352 |