John D. Carpten et al A transforming mutation in the pleckstrin homology domain of AKTl in cancer
Nature 2007, vol 448, 439-444
It is important for Nutritionists to appreciate the profound discoveries which are being made in Molecular Biology . There are so many naïve statements associating all manner of dietary excesses or deficiencies and cancer aetiology, based on epidemiological studies. To my mind these statements demean Nutrition in an increasingly sophisticated Scientific environment.
The enzyme AKTl (v-akt murine thymoma viral oncogene homologue 1) kinase is important in the most frequently proliferation and survival pathway in cancer, yet mutations of AKTl have not been reported. In the paper Carpten and his colleagues report the identification of a somatic mutation in human breast, colorectal and ovarian cancers that results in a glutamic acid to lysine substitution at amino acid 17 (E17K) in the lipid-binding pocket of AKTl. Lys17 alters the electrostatic interactions of the pocket and forms new hydrogen bonds with a phosphoinositide ligand. This mutation activates AKTl by means of pathological localization to the plasma membrane, stimulates downstream signalling, transforms cells and induces leukaemia in mice. This mechanism indicates a direct role of AKTl in human cancer, and adds to the known genetic alterations that promote oncogenesis through the phosphatidylinositol-3-OH kinase/AKT pathway.
- Martin Eastwood