Cell Signalling Survival

Recent studies have implicated Akt, a serine threonine kinase, as an important regulator of several cellular processes, including proliferation, metabolism and programmed cell death.  Akt activity is deregulated in a number of human malignancies in a variety of ways.  One of our goals is to identify and characterise the protein substrates of the kinase activity of Akt which are responsible for mediating its effect on cell behaviour.  We have identified Yes-associated protein, YAP, a transcription factor co-activator, as a substrate for Akt involved in signalling p73 regulated DNA-damage. We will profile the genes differentially regulated by YAP and other transcription factor targets effectors and effectors of Akt signalling such as Forkhead and p53 in the context of different DNA-damaging agents.  Specific roles of the resultant gene products will be investigated in particular apoptotic and activity state contexts.