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Accelerating increase in activity of human thymidine kinase 1 (TK1), providing thymidine monophosphate, accompanies the onset of S-phase during the cell cycle. This enzyme is also a prognostic and predictive factor for early stages of cancer, and the TK1 encoding genes are suitable as suicide genes in anti-cancer gene-therapy. TK1 has been reported to be able to switch between a dimer (with low activity) and a highly active tetramer. The latter form occurs only during S-phase where the enzyme concentration is high and ATP is present and this switch is very likely a crucial element in the tight regulation of the nucleic acid precursor pool. We would like to characterize a variety of TK1s, originating from bacteria, plants, lower animals and mammals, for their oligomerization and regulatory properties. Our main aim is to find out when in evolution the oligomerization regulatory switch originated, which amino acid residues are responsible for the oligomerisation of human TK1 and what is the oligomerisation role during the onset and progress of cancer.
Gæsteforsker ophold ved Lund Lund Universitet, COB hos Professor Jure Piskur