Probing new interaction partners for cop-per chaperones

Typ
Examensarbete för masterexamen
Master Thesis
Program
Biotechnology (MPBIO), MSc
Publicerad
2018
Författare
Valenzuela, Sebastian
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Sammanfattning
Copper (Cu) ions are cofactors found in many di˙erent proteins and are necessary for the proteins to be able to carry out their functions. However, Cu can also be harmful to cells as free Cu ions induce the formation reactive oxygen species, and Cu transfer is therefore closely regulated by special proteins called Cu chaperones. Cu is also connected to human disease as both Cu deficiency and Cu accumulation are harmful, and in recent years, Cu has emerged as a potential key factor in promotion of cancer as well. Since Cu chaperones are necessary for the distribution of Cu in cells, these proteins are also potential factors involved in Cu-dependent reactions in cancer. The purpose of this Master’s thesis, was to investigate if the Cu chaperones Atox1 and CCS could interact with either of the proteins MEK1, S100A12, and the domain of CPEB4 containing its RNA recognition motifs (CPEB4-RRM). These proteins have previously been linked to cancer involvement, and if they interact with Cu chaperones, it could explain the connection between Cu and cancer. The protein-protein interactions were studied by combining three di˙erent techniques: far-western blot, co-immunoprecipitation and surface plasmon resonance. The re-sults show that Atox1 is able to interact with all three proteins. The interaction to S100A12 is weak, and to CPEB4-RRM the interaction was detected only under specific conditions. MEK1 was able to interact with both Atox1 and CCS, with dis-sociation constants in micromolar range. Therefore, this thesis suggests that Atox1 and CCS are likely to deliver Cu to MEK1. This means both Atox1 and CCS are potential drug targets in treatments against cancer.
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Ämne/nyckelord
Livsvetenskaper , Biokemi och molekylärbiologi , Biofysik , Medicinsk bioteknologi (med inriktning mot cellbiologi) , Life Science , Biochemistry and Molecular Biology , Biophysics , Medical Biotechnology (with a focus on Cell Biology)
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