H2O2-dependent translocation of TCTP into the nucleus enables its interaction with VDR in human keratinocytes: TCTP as a further module in calcitriol signalling.
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.
Rid
Raphaela
R
Department of Cell Biology, Division of Genetics, University of Salzburg, Salzburg, Austria.
Onder
Kamil
K
Trost
Andrea
A
Bauer
Johann
J
Hintner
Helmut
H
Ritter
Markus
M
Jakab
Martin
M
Costa
Ivano
I
Reischl
Wolfgang
W
Richter
Klaus
K
MacDonald
Susan
S
Jendrach
Marina
M
Bereiter-Hahn
Jürgen
J
Breitenbach
Michael
M
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
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