Speaker: Jun-yuan Ji, associate professor at Texas A&M University Health Science Center, Department of Molecular and Cellular Medicine

Title: 'Context-specific functions of CDK8'

Abstract: Using the fruit fly Drosophila melanogaster and cultured mammalian cells as the experimental systems,we are interested in understanding the context-specific roles of the CDK8 module, a highly conserved module of the transcription cofactor Mediator complex, which bridges DNA-bound transcription factors and RNA polymerase II (Pol II) in eukaryotes. The four subunits of the CDK8 module - CDK8, Cyclin C, MED12, and MED13 - are either mutated or amplified in cardiovascular diseases and a number of human cancers. Elucidating the function and regulation of the CDK8 module in different biological contexts is essential to understanding the pathological consequences of its misregulation and to the design of clinical strategies to target the kinase activities of CDK8 in treating these diseases. We have identified two new downstream targets of CDK8, SREBP (sterol regulatory element-binding protein) and EcR (ecdysone receptor), as well as one upstream regulatory pathway of CDK8-CycC (the insulin/mTOR signaling pathway). Our results suggest that CDK8 coordinately regulates lipid biosynthesis by repressing SREBP-activated transcription and developmental timing by activating EcR-activated gene expression during the larval-pupal transition. Interestingly, CDK8 is stabilized by nutrient deprivation and destabilized by feeding, suggesting a novel link between dietary perturbations and the general transcriptional machinery. Furthermore, cdk8 mutants are hyper-sensitive to dietary perturbations, particularly proteins and several specific amino acids, likely through the inhibitory effects of mTOR on CDK8. Further analyses of CDK8 functions and regulation may advance our understanding of how dysregulation of the CDK8 module contributes tumorigenesis and other diseases.

Host: Hua Bai, GDCB assistant professor

Please join us for refreshments before the seminar outside Room 1414 of the Molecular Biology Building.