Research Interests

• Cyclin C-Cdk8 is a conserved transcriptional regulator that associates with the RNA polymerase II mediator complex. In response to stress, cyclin C (but not Cdk8) translocates from the nucleus to the mitochondria where it associates with the fission machinery. This process is conserved from yeast to man. Mitochondrial localization of cyclin C is required for both the extensive fission observed in stressed cells and efficient execution of programmed cell death. Our model is that cyclin C represents a stress-activated messenger that triggers hyperfission and loss of mitochondrial outer membrane permeability, two processes associated with programmed cell death. Loss of cyclin C activity protects both yeast and mammalian cells from oxidative stress and anti-cancer drug induced cell death. These findings, in combination with the loss of the cyclin C locus in many primary cancers, formally suggests that cyclin C represents a new tumor suppressor gene. This model is currently being tested using both cell culture models and our newly generated cyclin C knockout mouse.