Abstract #72

Stress-Induced Destruction of the Yeast C-type Cyclin Involves Nuclear Export and Mitochondrial Association. Katrina Cooper¹, Elizabeth Krasley², Grace Tan¹, Michael Mallory¹, Randy Strich¹. 1) Dept Molecular Biol, UMDNJ-SOM, Stratford, NJ; 2) Dupont Agriculture and Nutrition Group, Stein-Haskell Research Center, Newark DE.
   The yeast cyclin C-Cdk8 kinase represses stress response or meiotic gene transcription. To relieve this repression, cyclin C is destroyed in cells exposed to stress (e.g., heat shock, oxidative stress) or as they enter meiosis. In response to oxidative stress, cyclin C destruction requires phospholipase C (Pcl1p) and the Mpk1/Slt2p MAP kinase. This destruction is important as the hypersensitivity of plc1 and mpk1 mutants to oxidative stress is suppressed by deleting cyclin C. This study reveals that, prior to its destruction, cyclin C and Cdk8p are first exported from the nucleoplasm to the nucleolus. From there, only cyclin C translocates to the cytoplasm in a process that requires the exportin Msn5p and Cdk8p. Several results indicate that cyclin C nuclear export is tied to its degradation. First, stressors that do not induce cyclin C destruction (e.g., hyperosmolarity, nitrogen starvation) do not induce its export. In addition, Plc1p and Mpk1/Slt2 are required for the nucleoplasm to nucleolus translocation. In the cytoplasm, both cytological and biochemical studies revealed that cyclin C form foci that associate with the mitochondria. This localization is important for destruction as artificially targeting cyclin C to the mitochondria induced its degradation in the absence of stress. This study describes a new stress-activated cyclin degradation pathway that requires complex subcellular relocalization and mitochondrial associated proteolysis.

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