SUMOylation of HNF4α regulates protein stability and hepatocyte function
The coordination of signalling pathways within the cell is vital for normal human development and post-natal tissue homeostasis. Gene expression and function is therefore tightly controlled at a number of levels. We investigated the role that post-translational modifications play during human hepato...
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The Company of Biologists
2012
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445325/ |
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pubmed-34453252012-11-15 SUMOylation of HNF4α regulates protein stability and hepatocyte function Zhou, Wenli Hannoun, Zara Jaffray, Ellis Medine, Claire N. Black, James R. Greenhough, Sebastian Zhu, Liang Ross, James A. Forbes, Stuart Wilmut, Ian Iredale, John P. Hay, Ronald T. Hay, David C. Research Article The coordination of signalling pathways within the cell is vital for normal human development and post-natal tissue homeostasis. Gene expression and function is therefore tightly controlled at a number of levels. We investigated the role that post-translational modifications play during human hepatocyte differentiation. In particular, we examined the role of the small ubiquitin-like modifier (SUMO) proteins in this process. We used a human embryonic stem cell (hESC)-based model of hepatocyte differentiation to follow changes in protein SUMOylation. Moreover, to confirm the results derived from our cell-based system, we performed in vitro conjugation assays to characterise SUMO modification of a key liver-enriched transcription factor, HNF4α. Our analyses indicate that SUMOylation plays an important role during hepatocellular differentiation and this is mediated, in part, through regulation of the stability of HNF4α in a ubiquitin-dependent manner. Our study provides a better understanding of SUMOylation during human hepatocyte differentiation and maturation. Moreover, we believe the results will stimulate interest in the differentiation and phenotypic regulation of other somatic cell types. The Company of Biologists 2012-08-01 /pmc/articles/PMC3445325/ /pubmed/22505616 http://dx.doi.org/10.1242/jcs.102889 Text en © 2012. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0/), which permits unrestricted non-commercial use, distribution and reproduction in any medium providedthat the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms. |
| 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 |
Zhou, Wenli Hannoun, Zara Jaffray, Ellis Medine, Claire N. Black, James R. Greenhough, Sebastian Zhu, Liang Ross, James A. Forbes, Stuart Wilmut, Ian Iredale, John P. Hay, Ronald T. Hay, David C. |
| spellingShingle |
Zhou, Wenli Hannoun, Zara Jaffray, Ellis Medine, Claire N. Black, James R. Greenhough, Sebastian Zhu, Liang Ross, James A. Forbes, Stuart Wilmut, Ian Iredale, John P. Hay, Ronald T. Hay, David C. SUMOylation of HNF4α regulates protein stability and hepatocyte function |
| author_facet |
Zhou, Wenli Hannoun, Zara Jaffray, Ellis Medine, Claire N. Black, James R. Greenhough, Sebastian Zhu, Liang Ross, James A. Forbes, Stuart Wilmut, Ian Iredale, John P. Hay, Ronald T. Hay, David C. |
| author_sort |
Zhou, Wenli |
| title |
SUMOylation of HNF4α regulates protein stability and hepatocyte function |
| title_short |
SUMOylation of HNF4α regulates protein stability and hepatocyte function |
| title_full |
SUMOylation of HNF4α regulates protein stability and hepatocyte function |
| title_fullStr |
SUMOylation of HNF4α regulates protein stability and hepatocyte function |
| title_full_unstemmed |
SUMOylation of HNF4α regulates protein stability and hepatocyte function |
| title_sort |
sumoylation of hnf4α regulates protein stability and hepatocyte function |
| description |
The coordination of signalling pathways within the cell is vital for normal human development and post-natal tissue homeostasis. Gene expression and function is therefore tightly controlled at a number of levels. We investigated the role that post-translational modifications play during human hepatocyte differentiation. In particular, we examined the role of the small ubiquitin-like modifier (SUMO) proteins in this process. We used a human embryonic stem cell (hESC)-based model of hepatocyte differentiation to follow changes in protein SUMOylation. Moreover, to confirm the results derived from our cell-based system, we performed in vitro conjugation assays to characterise SUMO modification of a key liver-enriched transcription factor, HNF4α. Our analyses indicate that SUMOylation plays an important role during hepatocellular differentiation and this is mediated, in part, through regulation of the stability of HNF4α in a ubiquitin-dependent manner. Our study provides a better understanding of SUMOylation during human hepatocyte differentiation and maturation. Moreover, we believe the results will stimulate interest in the differentiation and phenotypic regulation of other somatic cell types. |
| publisher |
The Company of Biologists |
| publishDate |
2012 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445325/ |
| _version_ |
1611909784637800448 |