title: Multiple post-translational modifications in hepatocyte nuclear factor 4α.
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 mass-spectrometry 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.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Shogo
authors.initials: S
authors.lastname: Katsura
authors.forename: Ryo
authors.initials: R
authors.lastname: Ito
authors.forename: Waka
authors.initials: W
authors.lastname: Hashiba
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sekine
authors.forename: Ryoji
authors.initials: R
authors.lastname: Fujiki
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D056945:Hep G2 Cells; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015533:Transcriptional Activation / Q000235:genetics; D054875:Ubiquitination
chemical_list: C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D008239:Lysine