Regulation of protein translation and cell cycle processes by reversible protein phosphorylation in response to dehydration in the African clawed frog
The primarily aquatic African clawed frog, Xenopus laevis, has adapted to endure substantial dehydration, partly by entering a state of hypometabolism. This thesis focuses on two processes targeted by the central protein kinase Akt (that is inhibited during dehydration) – protein translation and the cell cycle. Results suggest that dehydration leads to mTORC1 inhibition via PRAS40 activation in both liver and skeletal muscle, thereby suppressing protein synthesis. Suppression of Akt also allows activation of p21 and p27 cell cycle inhibitors to promote cell cycle arrest in liver. Analysis of multiple protein components shows that cell cycle arrest is actively facilitated in liver, but not in muscle. Regulation of liver kinases and phosphatases led to hypophosphorylation of Rb which inhibits E2F1-induced transcription of genes required for cell cycle progression. Overall, during dehydration, frogs suppress protein translation in liver and muscle, and show regulated cell cycle arrest in liver, a proliferative tissue.