title: Nuclear import of a lipid-modified transcription factor: mobilization of NFAT5 isoform a by osmotic stress.
abstract: Lipid-modified transcription factors (TFs) are biomolecular oddities since their reduced mobility and membrane attachment appear to contradict nuclear import required for their gene-regulatory function. NFAT5 isoform a (selected from an in silico screen for predicted lipid-modified TFs) is shown to contribute about half of all endogenous expression of human NFAT5 isoforms in the isotonic state. Wild-type NFAT5a protein is indeed myristoylated and palmitoylated on its transport to the plasmalemma via the endoplasmic reticulum and the Golgi. In contrast, its lipid anchor-deficient mutants as well as isoforms NFAT5b/c are diffusely localized in the cytoplasm without preference to vesicular structures. Quantitative/live microscopy shows the plasmamembrane-bound fraction of NFAT5a moving into the nucleus upon osmotic stress despite the lipid anchoring. The mobilization mechanism is not based on proteolytic processing of the lipid-anchored N-terminus but appears to involve reversible palmitoylation. Thus, NFAT5a is an example of TFs immobilized with lipid anchors at cyotoplasmic membranes in the resting state and that, nevertheless, can translocate into the nucleus upon signal induction.
authors.affiliation: Bioinformatics Institute, A*STAR, Singapore.
authors.forename: Birgit
authors.initials: B
authors.lastname: Eisenhaber
authors.forename: Michaela
authors.initials: M
authors.lastname: Sammer
authors.forename: Wai Heng
authors.initials: WH
authors.lastname: Lua
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Benetka
authors.forename: Lai Ling
authors.initials: LL
authors.lastname: Liew
authors.forename: Weimiao
authors.initials: W
authors.lastname: Yu
authors.forename: Hwee Kuan
authors.initials: HK
authors.lastname: Lee
authors.forename: Manfred
authors.initials: M
authors.lastname: Koranda
authors.forename: Frank
authors.initials: F
authors.lastname: Eisenhaber
authors.forename: Sharmila
authors.initials: S
authors.lastname: Adhikari
mesh_terms: D021581:Active Transport, Cell Nucleus; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D009997:Osmotic Pressure; D020033:Protein Isoforms / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008055:Lipids; C118125:NFAT5 protein, human; D020033:Protein Isoforms; D014157:Transcription Factors
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