Title | SUMOylation of HNF4α regulates protein stability and hepatocyte function. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Zhou 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 |
Journal | J Cell Sci |
Volume | 125 |
Issue | Pt 15 |
Pagination | 3630-5 |
Date Published | 2012 Aug 1 |
ISSN | 1477-9137 |
Keywords | Catalytic 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. |
DOI | 10.1242/jcs.102889 |
Alternate Journal | J. Cell. Sci. |
PubMed ID | 22505616 |
PubMed Central ID | PMC3445325 |
Grant List | / / Cancer Research UK / United Kingdom / / Medical Research Council / United Kingdom |