Trefoil Factor 1 is involved in gastric cell copper homeostasis |
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| Affiliation: | 1. Department of Pharmacy, University of Salerno, Fisciano, SA, Italy;2. Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy;3. Department of Chemistry and Biology, University of Salerno, Fisciano, SA, Italy;1. Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA;2. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA;3. School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Queensland 4072, Australia;4. Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia;1. Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary;2. Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary;1. Yeast Molecular Genetics Lab, Institute of Molecular Biology “R. Tsanev”, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria;2. Laboratory of Biophysical Chemistry, Department of Physical Chemistry, Faculty of Chemistry and Pharmacy, Sofia University “St. Kliment Ohridski”, Sofia 1164, Bulgaria;3. Laboratory of Molecular Biology, Department of Molecular and Cell Biology, Division of Life Science, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan;1. Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, United States;2. Virogene Technology, 11000 Cedar Ave., Cleveland, OH, United States;3. Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, United States |
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| Abstract: | Trefoil Factor 1 belongs to a group of small secreted proteins (the Trefoil Factor Family proteins), that are localized within the mucous granules and are expressed and secreted by epithelial cells that line mucous membranes. Trefoil factors are mainly expressed in the gastrointestinal tract, where they normally contribute to maintain the integrity of the mucosa. We recently demonstrated a selective binding ability of Trefoil Factor 1 for copper ions, through its carboxy-terminal tail, and we also observed that copper levels influence the equilibrium between the monomeric and homodimeric forms of Trefoil Factor 1, thus modulating its biological activity. Here we report that transcriptional regulation of Trefoil Factor 1 is also affected by copper levels, through the modulated binding of the copper-sensing transcription factor Sp1 onto the responsive elements present in the regulatory region of the gene. In addition we demonstrate that copper overload causes an accumulation of the trefoil protein in the Trans-Golgi Network and that Trefoil Factor 1 levels can influence copper excretion and copper related toxicity. These findings suggest that the protein might play a role in the overall complex mechanisms of copper homeostasis in the gastrointestinal tissues. |
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| Keywords: | Trefoil factors TFF1 Copper Sp1 |
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