Multiple post-translational modifications in hepatocyte nuclear factor 4α

Atsushi Yokoyama, Shogo Katsura, Ryo Ito, Waka Hashiba, Hiroki Sekine, Ryoji Fujiki, Shigeaki Kato

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

To investigate the role of post-translational modifications (PTMs) in the hepatocyte nuclear factor 4α (HNF4α)-mediated transcription, we took a comprehensive survey of PTMs in HNF4α protein by massspectrometry and identified totally 8 PTM sites including newly identified ubiquitilation and acetylation sites. To assess the impact of identified PTMs in HNF4α-function, we introduced point mutations at the identified PTM sites and, tested transcriptional activity of the HNF4α. Among the point-mutations, an acetylation site at lysine 458 was found significant in the HNF4α-mediated transcriptional control. An acetylation negative mutant at lysine 458 showed an increased transcriptional activity by about 2-fold, while an acetylation mimic mutant had a lowered transcriptional activation. Furthermore, this acetylation appeared to be fluctuated in response to extracellular nutrient conditions. Thus, by applying an comprehensive analysis of PTMs, multiple PTMs were newly identified in HNF4α and unexpected role of an HNF4α acetylation could be uncovered.

Original languageEnglish
Pages (from-to)749-753
Number of pages5
JournalBiochemical and biophysical research communications
Volume410
Issue number4
DOIs
Publication statusPublished - 2011 Jul 15
Externally publishedYes

Keywords

  • Acetylation
  • Hepatocyte nuclear factor 4α
  • Post-translational modification

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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