The Department of Biomedicine

BBB seminar: Thomas Arnesen

Combining basic and translational research - Experiences from the Bergen NAT-project

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Thomas Arnesen
Department of Biomedicine, University of Bergen

Based on a Norwegian biobank investigation, a novel gene, NAA15 (NATH), was found to be upregulated in thyroid tumor tissues as compared to non-tumor tissues, in particular in aggressive and undifferentiated tumors. Since then, researchers at UiB and HUS have investigated the basic biochemical and cellular functions of NAA15 and a number of related proteins. NAA15 and its partner NAA10 forms the N-terminal acetyltransferase A (NatA) complex which is responsible for acetylating proteins at their N-terminal end. Depletion of NatA from cancer cells induces apoptosis, cell cycle arrest, and sensitizes cells for chemotherapy. Thus, NatA may be a potential anti-cancer drug target and selective inhibitors are under development. Also, mutations in the NAA10 and NAA15 genes are emerging as causative for congenital anomalies, including intellectual disability and cardiac arrhythmia. The NatA complex was the first member of a machinery of seven uncovered NAT-enzymes operating in human cells which, in combination, acetylate 80-90% of all cellular proteins. These NATs have different substrates and impact cells and organisms in various ways. The most recently discovered enzyme specifically targets a cytoskeleton component and regulates cell motility, and this is now being further pursued in a translational setting.

Chairperson: Stein Ove Døskeland, Department of Biomedicine