Multiple post-translational modifications in hepatocyte nuclear factor 4 alpha

作者：Yokoyama Atsushi; Katsura Shogo; Ito Ryo; Hashiba Waka; Sekine Hiroki; Fujiki Ryoji; Kato Shigeaki^*

来源：Biochemical and Biophysical Research Communications, 2011, 410(4): 749-753.

DOI：10.1016/j.bbrc.2011.06.033

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

To investigate the role of post-translational modifications (PTMs) in the hepatocyte nuclear factor 4 alpha (HNF4 alpha)-mediated transcription, we took a comprehensive survey of PTMs in HNF4 alpha 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 HNF4 alpha-function, we introduced point mutations at the identified PTM sites and, tested transcriptional activity of the HNF4 alpha. Among the point-mutations, an acetylation site at lysine 458 was found significant in the HNF4 alpha-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 HNF4 alpha and unexpected role of an HNF4 alpha acetylation could be uncovered.

• 出版日期2011-7-15