SUMOylation of HNF4α Regulates Protein Stability and Hepatocyte Function

Wenli Zhou, Zara Hannoun, Ellis Jaffray, Claire N. Medine, James R. Black, Sebastian Greenhough, Liang Zhu, James A. Ross, Stuart Forbes, Ian Wilmut, John P. Iredale, Ronald T. Hay, David C. Hay*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)3630-3635
Number of pages6
JournalJournal of Cell Science
Volume125
Issue number15
DOIs
Publication statusPublished - 1 Aug 2012

Keywords

  • Hepatocyte
  • p450
  • BINDING
  • HNF4 alpha
  • SUMO
  • UBIQUITIN LIGASE
  • hESCs
  • DIFFERENTIATION
  • ACTIVATION
  • RNF4
  • Cell-based modelling
  • Transthyretin
  • HUMAN BLASTOCYSTS
  • Liver
  • DOMAIN
  • Ubiquitin
  • STEM-CELL LINES

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