PMU-Autor/inn/en
Bauer JohannAbstract
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.
Useful keywords (using NLM MeSH Indexing)
Active Transport, Cell Nucleus/drug effects
Active Transport, Cell Nucleus/physiology
Calcitriol/pharmacology
Calcitriol/physiology*
Cell Line, Transformed
Cell Nucleus/metabolism*
Cytoplasm/metabolism
DNA/metabolism
Electrophoretic Mobility Shift Assay
Feedback, Physiological/physiology
Fluorescence Resonance Energy Transfer
Gene Expression/genetics
Gene Expression Regulation, Neoplastic/physiology
Humans
Hydrogen Peroxide/pharmacology*
Immunoprecipitation
Keratinocytes/drug effects
Keratinocytes/metabolism*
Oxidative Stress/drug effects
Oxidative Stress/physiology
Promoter Regions, Genetic/genetics
Protein Binding/drug effects
Protein Binding/physiology
Protein Interaction Domains and Motifs/physiology
Receptors, Calcitriol/genetics
Receptors, Calcitriol/metabolism*
Recombinant Proteins/metabolism
Signal Transduction/drug effects
Signal Transduction/physiology*
Tumor Markers, Biological/genetics
Tumor Markers, Biological/metabolism*
Two-Hybrid System Techniques
Vitamin D Response Element/genetics
Find related publications in this database (Keywords)
TCTP