title: H2O2-dependent translocation of TCTP into the nucleus enables its interaction with VDR in human keratinocytes: TCTP as a further module in calcitriol signalling.
abstract: Translationally controlled tumour protein (TCTP) is an evolutionarily highly conserved molecule implicated in many processes related to cell cycle progression, proliferation and growth, to the protection against harmful conditions including apoptosis and to the human allergic response. We are showing here that after application of mild oxidative stress, human TCTP relocates from the cytoplasm to the nuclei of HaCaT keratinocytes where it directly associates with the ligand-binding domain of endogenous vitamin D(3) receptor (VDR) through its helical domain 2 (AA 71-132). Interestingly, the latter harbours a putative nuclear hormone receptor coregulatory LxxLL-like motif which seems to be involved in the interaction. Moreover, we demonstrate that VDR transcriptionally induces the expression of TCTP by binding to a previously unknown VDR response element within the TCTP promotor. Conversely, ectopically overexpressed TCTP downregulates the amount of VDR on both mRNA as well as protein level. These data, to conclude, suggest a kind of feedback regulation between TCTP and VDR to regulate a variety of (Ca(2+) dependent) cellular effects and in this way further underscore the physiological relevance of this novel protein-protein interaction.
authors.affiliation: Department of Cell Biology, Division of Genetics, University of Salzburg, Salzburg, Austria.
authors.forename: Raphaela
authors.initials: R
authors.lastname: Rid
authors.forename: Kamil
authors.initials: K
authors.lastname: Onder
authors.forename: Andrea
authors.initials: A
authors.lastname: Trost
authors.forename: Johann
authors.initials: J
authors.lastname: Bauer
authors.forename: Helmut
authors.initials: H
authors.lastname: Hintner
authors.forename: Markus
authors.initials: M
authors.lastname: Ritter
authors.forename: Martin
authors.initials: M
authors.lastname: Jakab
authors.forename: Ivano
authors.initials: I
authors.lastname: Costa
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Reischl
authors.forename: Klaus
authors.initials: K
authors.lastname: Richter
authors.forename: Susan
authors.initials: S
authors.lastname: MacDonald
authors.forename: Marina
authors.initials: M
authors.lastname: Jendrach
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bereiter-Hahn
authors.forename: Michael
authors.initials: M
authors.lastname: Breitenbach
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology / Q000502:physiology*; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D025461:Feedback, Physiological / Q000502:physiology; D031541:Fluorescence Resonance Energy Transfer; D015870:Gene Expression / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D047468:Immunoprecipitation; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000090324:Tumor Protein, Translationally-Controlled 1; D020798:Two-Hybrid System Techniques; D030181:Vitamin D Response Element / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018167:Receptors, Calcitriol; D011994:Recombinant Proteins; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; D004247:DNA; D006861:Hydrogen Peroxide; D002117:Calcitriol