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SUMOylation of HNF4α regulates protein stability and hepatocyte function.

TitleSUMOylation of HNF4α regulates protein stability and hepatocyte function.
Publication TypeJournal Article
Year of Publication2012
AuthorsZhou W, Hannoun Z, Jaffray E, Medine C.N, Black JR, Greenhough S, Zhu L, Ross JA, Forbes SJ, Wilmut I, Iredale JP, Hay RT, Hay DC
JournalJ Cell Sci
Volume125
IssuePt 15
Pagination3630-5
Date Published2012 Aug 1
ISSN1477-9137
KeywordsCatalytic Domain, Cell Differentiation, Embryonic Stem Cells, Hepatocyte Nuclear Factor 4, Hepatocytes, Humans, Nuclear Proteins, Oxidative Stress, Protein Stability, Signal Transduction, Small Ubiquitin-Related Modifier Proteins, Sumoylation, Transcription Factors, Ubiquitination
Abstract

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.

DOI10.1242/jcs.102889
Alternate JournalJ. Cell. Sci.
PubMed ID22505616
PubMed Central IDPMC3445325
Grant List / / Cancer Research UK / United Kingdom
/ / Medical Research Council / United Kingdom