Copper homeostasis (Homo sapiens)
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Description
Copper is a redox-active transition metal and an essential trace element for life. It is a catalytic cofactor for numerous enzymes involved in critical biological processes (e.g. detoxification by oxygen free radicals, angiogenesis, pigmentation, peptide hormone production, etc.). However, "free" copper is harmful for cells because it can generate ROS that leads to cellular damage. Thus, all organisms and cells maintain a tight control of its uptake, trafficking and export. This process is rather intricate and requires an interplay between numerous biomolecules (e.g. proteins, metabolites) that act as copper ions importers (CTR1, CTR2, DMT1, Prp, APP), chaperones (CCS, ATOX1, COX17, COMMD1) and exporters (ATP7A, ATP7B). Copper ions and Cu-independent stimuli (hormone, oxygen, phosphorylation and ubiquination) seem to affect localization and expression of Cu-transporters and chaperones. Potential targets of copper ions seem to be crucial signaling pathways, such as PI3K/Akt, in which copper induces insulin-like effects. Copper dyshomeostasis could be implicated in cancer and a number of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, prion disease and ALS.
Proteins on this pathway have targeted assays available via the CPTAC Assay Portal
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Bibliography
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- Ba LA, Doering M, Burkholz T, Jacob C; ''Metal trafficking: from maintaining the metal homeostasis to future drug design.''; Metallomics, 2009 PubMed Europe PMC Scholia
- Kim BE, Nevitt T, Thiele DJ; ''Mechanisms for copper acquisition, distribution and regulation.''; Nat Chem Biol, 2008 PubMed Europe PMC Scholia
- Nevitt T, Ohrvik H, Thiele DJ; ''Charting the travels of copper in eukaryotes from yeast to mammals.''; Biochim Biophys Acta, 2012 PubMed Europe PMC Scholia
- Song IS, Chen HH, Aiba I, Hossain A, Liang ZD, Klomp LW, Kuo MT; ''Transcription factor Sp1 plays an important role in the regulation of copper homeostasis in mammalian cells.''; Mol Pharmacol, 2008 PubMed Europe PMC Scholia
- Mufti AR, Burstein E, Duckett CS; ''XIAP: cell death regulation meets copper homeostasis.''; Arch Biochem Biophys, 2007 PubMed Europe PMC Scholia
- Lutsenko S; ''Human copper homeostasis: a network of interconnected pathways.''; Curr Opin Chem Biol, 2010 PubMed Europe PMC Scholia
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