Multiple post-translational modifications in hepatocyte nuclear factor 4alpha.
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Yokoyama A, Katsura S, Ito R, Hashiba W, Sekine H, Fujiki R, Kato S
Multiple post-translational modifications in hepatocyte nuclear factor 4alpha.
Biochem Biophys Res Commun. 2011 Jul 15;410(4):749-53. doi: 10.1016/j.bbrc.2011.06.033. Epub 2011 Jun 17.
- PubMed ID
- 21708125 [ View in PubMed]
- Abstract
To investigate the role of post-translational modifications (PTMs) in the hepatocyte nuclear factor 4alpha (HNF4alpha)-mediated transcription, we took a comprehensive survey of PTMs in HNF4alpha protein by mass-spectrometry and identified totally 8 PTM sites including newly identified ubiquitilation and acetylation sites. To assess the impact of identified PTMs in HNF4alpha-function, we introduced point mutations at the identified PTM sites and, tested transcriptional activity of the HNF4alpha. Among the point-mutations, an acetylation site at lysine 458 was found significant in the HNF4alpha-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 HNF4alpha and unexpected role of an HNF4alpha acetylation could be uncovered.